Biomedical subjects
Publications and source records attributed to H Davidson.
The course of anorexia nervosa frequently has episodes of exacerbation during which motivation and insight are reduced, cognition is impaired and treatment resistance is increased. Formalizing a directive to be used during these episodes when the patient has greater motivation and insight is one way of reducing treatment resistance. We describe a form of directive, called the "Ulysses Agreement".
To test the hypothesis that periosteal circumference (PC), which is associated with bone size through cross-sectional moment of inertia (CMI), has heritable components, we performed a linkage analysis using 633 MRL/SJL F(2) mice that have 14% difference in mean PC. PC was determined in femurs by use of peripheral quantitative computerized tomography (pQCT). The genome-wide scan identified nine QTL for PC adjusted by body weight on chromosomes 1 (2 QTL), 2 (2 QTL), 8, 11, 15, 17, and X, which accounted for 38.6% of phenotype variance. QTL on chromosomes 1 (D1Mit33), 8 (D8Mit125), 15 (D15Mit 62), 17 (D17Mit176), and X (DXMit208) were unique for PC adjusted by body weight and femur length, while the remaining PC QTL were shared with body weight but not femur length. Four epistatic interactions were identified which accounted for 37.6% of phenotype variance. There was also evidence of pleiotropic effects on chromosome 11 among four size phenotypes (PC, body length, body weight, bone mineral density, and muscle size), which may represent a common genetic mechanism that may regulate bone size and body size.
A novel method of family therapy for persons suffering from eating disorders, therapeutic letter writing (TLR), is presented. The protocol used for letter writing, its advantages and limitations, and a variety of applications are reviewed. The concept of TLR grew out of the study of narrative therapy, and was strongly influenced by ideas of Lorraine Wright and Maureeen Leahey about nurses and families, as well as the work of W.R. Miller around stages of change. This article will review: the process of TLR; therapeutic uses of eating disorders linked to TLR, including those relevant to families divided by distance or understanding; and the advantanges and disadvantages of TLR. Finally, a case study is discussed.
Studies on genetic mechanisms of wound healing in mammals are very few, although injury is a leading cause of the global burden of disease. In this study, we performed a high-density, genome-wide scan using 633 (MRL/MPJ x SJL/J) F(2) intercross at multiple time points (days 15, 21, and 25) to identify quantitative trait loci (QTL) involved in wound healing/regeneration. The hypothesis of the study was that QTL and unique epistatic interactions are involved at each time point to promote wound healing/regeneration. Ten QTL were identified from chromosomes 1, 4, 6, 7, 9, and 13. Of the 10 QTL, eight from chromosomes 1, 4, 6, and 9 were novel as compared to QTL identified in the study. The 10 QTL altogether explained 70% of variance in F(2) mice. The same QTL were identified at each time point, with simple linear correlation between days 15, 21, and 25, showing very high significant relationships (R >0.92, P <0.0001). Unique epistatic interactions were identified at each time point except those from chromosomes 4, 6, 9, and 13 that were found at all three time points, showing that some loci are involved at all the three time points of wound healing (days 15, 21, and 25). Therefore, loci-to-loci interactions may play a major role in wound healing. Information from these studies may help in the identification of genes that could be involved in wound healing/regeneration.
This paper provides a legal and ethical analysis of some controversial aspects of a recent proposal for an independent audit of New Zealand's National Cervical Screening Programme. The analysis reveals the difficulties likely to arise between investigators and ethics committees when the interests served by important public health research compete with the rigorous protection of patients' privacy.
PURPOSE: To compare results of 2 statistical methods for identifying factors in claims data that are associated with switching insurance plans between managed care (MC) and indemnity (IN).METHODS: Using claims data from 2 insurance providers in a northeastern city, we analyzed patients aged 18+ with diabetes, asthma, or congestive heart failure (CHF) who were covered any time in 1993-1997 (N = 88,917). Stratifying by initial plan type, we examined predictors of switching from the initial plan type using logistic regression and survival analysis. Covariates included age, time in study (for logistic models), gender, diabetes (yes/no), CHF (yes/no), and asthma (yes/no). Survival analysis accounted for time to switch and allowed time-varying covariates.RESULTS: In logistic regression models, older individuals who were in IN were much less likely to switch into MC. Those in MC were more likely to switch to IN, with the greatest likelihood of switching in ages 60-69 (OR = 4.00, 95% CI = 3.32-4.83). Females were less likely to switch from IN to MC (OR = 0.92, 95% CI = 0.87-0.98), CHF patients were less likely to switch from IN to MC (OR = 0.75, 95% CI = 0.68-0.83), and diabetes patients were less likely to switch from MC to IN (OR = 0.77, 95% CI = 0.62-0.96). Hazard ratios calculated using Cox regression were similar to odds ratios for most covariates. However, some coefficients for diseases were significant in Cox models but not in the logistic models. Cox models took 45 times longer in CPU time than logistic regression models.CONCLUSIONS: Logistic regression was a good approximation to Cox regression in identifying many of the factors in switching insurance plan in these data, at a fraction of the computing time. However, Cox models allowed diseases to be time-varying, and so was more sensitive to identifying significant relationships with disease.
Two cognitive tasks (a letter memory task and a spatial memory task) designed to selectively activate the left or right hemisphere were combined with attentional probe tasks to measure how hemispheric activation affects attention to left and right hemifields. The probe task in Experiment 1 required the identification of digits in the left and right hemifield. During the letter task, male subjects identified more probes from the left hemifield than from the right. Their accuracy varied little across the two hemifields during the dots task. Experiment 2 tested whether this pattern is due to either spatial attention or interference in character processing. Instead of identifying digits, the probe task required subjects to respond to a black square that appeared in the periphery of the screen. For male subjects, the pattern was opposite of that from Experiment 1. During the letter task they responded faster to the probe in the right hemifield than in the left. Their response times were equivalent across the two hemifields during the dots task.These results indicate two separate effects of laterality in male subjects. The activation of one hemisphere produced more attention to the contralateral hemifield in Experiment 2, and the letter memory task interfered with the processing of other characters in the right visual field more than those in the left visual field in Experiment 1. Neither of these effects appeared in female subjects, corroborating earlier claims that female brains are less lateralized than male brains.
To define control elements that regulate tissue-specific expression of the cystic fibrosis transmembrane regulator (CFTR), we have sequenced 60 kb of genomic DNA from the puffer fish Fugu rubripes (Fugu) that includes the CFTR gene. This region of the Fugu genome shows conservation of synteny with 800-kb sequence of the human genome encompassing the WNT2, CFTR, Z43555, and CBP90 genes. Additionally, the genomic structure of each gene is conserved. In a multiple sequence alignment of human, mouse, and Fugu, the putative WNT2 promoter sequence is shown to contain highly conserved elements that may be transcription factor or other regulatory binding sites. We have found two putative ankyrin repeat-containing genes that flank the CFTR gene. Overall sequence analysis suggests conservation of intron/exon boundaries between Fugu and human CFTR and revealed extensive homology between functional protein domains. However, the immediate 5' regions of human and Fugu CFTR are highly divergent with few conserved sequences apart from those resembling diminished cAMP response elements (CRE) and CAAT box elements. Interestingly, the polymorphic polyT tract located upstream of exon 9 is present in human and Fugu but absent in mouse. Similarly, an intron 1 and intron 9 element common to human and Fugu is absent in mouse. The euryhaline killifish CFTR coding sequence is highly homologous to the Fugu sequence, suggesting that upregulation of CFTR in that species in response to salinity may be regulated transcriptionally.
OBJECTIVE: To determine whether the tears of llamas, sheep, and cattle contain lysozyme and compare lysozyme concentrations in tears among these species. ANIMALS: 40 llamas, 5 sheep, and 36 cattle. PROCEDURE: Electrophoresis, western blot immunoassay for lysozyme, a spectrophotometric assay to detect tear lysozyme by its ability to lyse a suspension of Micrococcus lysodeiticus, and a microtiter plate colorometric assay were performed. RESULTS: A 13.6-kd protein band was detected by use of electrophoresis and western blot immunoassay in llama and sheep tears but not cattle tears. Results of spectrophotometric assay suggested that llama and sheep tears had high concentrations of lysozyme, whereas cattle tears had low concentrations. Results of the microtiter plate colorometric assay suggested that llama tears had high concentrations of lysozyme, whereas concentrations in sheep and cattle tears were lower. CONCLUSIONS AND CLINICAL RELEVANCE: Lysozyme concentrations in tears may vary among species and this variability may contribute to differing susceptibilities to ocular diseases such as infectious keratoconjunctivitis.
BACKGROUND: The concentration of thiamin diphosphate (TDP) in erythrocytes is a useful index of thiamin status. We describe an HPLC method for TDP and its results in patients at risk of thiamin deficiency. METHODS: We used reversed-phase HPLC with postcolumn derivatization with alkaline potassium ferricyanide and fluorescence detection. Samples were deproteinized and injected directly onto a C(18) column. TDP concentrations in erythrocytes were compared with those in whole blood. Reference intervals for erythrocyte TDP (n = 147; 79 males and 68 females; mean age, 54 years) and whole blood TDP (n = 124; 68 males and 56 females; mean age, 54 years) were determined in an apparently healthy population. We compared erythrocyte TDP with results of the erythrocyte transketolase activation test in 63 patients who were considered at risk of thiamin deficiency. RESULTS: The method was linear to at least 200 microgram/L. The between-run CV was <8%. The lower limit of quantification for both whole blood and packed erythrocytes was 300 pg on column with a detection limit of 130 pg on column. Recovery of TDP from blood samples was >90%. TDP in erythrocytes correlated strongly with that in whole blood (r = 0.97). Reference intervals for erythrocyte and whole blood TDP were 280-590 ng/g hemoglobin and 275-675 ng/g hemoglobin, respectively. Of the 63 patients suspected of thiamin deficiency, 46 were normal by both TDP and activation tests, 13 were deficient by both tests, 1 was deficient by the activation test but had normal erythrocyte TDP concentrations, and 4 were normal by the activation test but had low TDP. CONCLUSIONS: The HPLC method is precise and yields results similar to the erythrocyte activation assay.
SETTING: Six New York State Department of Health tuberculosis (TB) directly observed therapy (DOT) programs in public, private and community facilities in New York City. OBJECTIVE: A key feature of the TB DOT program was provision of incentives to motivate patients and increase adherence to therapy. The study hypothesis was that adherence will improve as the value of incentives increases and bonuses are added in a schedule of increasing rewards. DESIGN: The study population consisted of 365 patients in six inner city TB DOT programs. Interviews, clinical data and attendance records for 3+ years were analyzed. RESULTS: Patients who adhered (attending 80% of prescribed DOT visits each month of treatment) and those who did not were similar on seven demographic factors (e.g., age and sex), but were significantly different on clinical and social variables. Previous TB, resistance to rifampin, human immunodeficiency virus infection, psychiatric illness, homelessness, smoking and drug use were related to non-adherence. High adherence was significantly associated with fewer months in treatment (P < 0.016). Logistic regression showed that the odds that a patient would adhere to therapy were greater with increased incentives. Odds of adherence were significantly lower with rifampin resistance and psychiatric illness. CONCLUSION: Increasing incentives is associated with improved adherence to therapy in inner city TB populations.
The subcloning of large inserts (>50 kbp) from P1-derived artificial chromosomes (PACs) was found to be hindered by the presence of contaminating Escherichia coli chromosomal fragments which, because of their smaller median size, are recovered preferentially as unwanted subclones. A significant fraction of contaminating DNA was seen to persist after conventional plasmid purification methods. We describe a rigorous protocol for eliminating the bulk of contamination that involves plasmid isolation on commercially available silica-based columns followed by three pulsed field gel electrophoresis steps. Using this, we were able to subclone 55, 85 and 90 kbp PAC inserts but failed to subclone a 195 kbp PAC insert. After surveying a range of DNA purification methods, we devised an optimised protocol that allowed us to subclone the 195 kbp insert. The optimised protocol, which reliably yields DNA with essentially no contaminating material, consists of plasmid isolation on silica-based columns followed by treatment with highly purified DNaseI and retrieval by electroelution of restriction-digested DNA electrophoresed on a single pulsed field gel. By inference it is applicable to the purification of large inserts from other single-copy plasmid vectors such as bacterial artificial chromosomes (BACs).
OBJECTIVES: This study examined patients' satisfaction with New York State's tuberculosis (TB) directly observed therapy (DOT) programs in New York City. METHODS: A survey was conducted of 435 patients at 19 public, private, and community-based TB DOT clinics about their satisfaction with various aspects of the programs. RESULTS: Patients identified the opportunity to receive good medical care as the most important aspect of TB DOT. Also significant was the supportiveness of DOT staff. Receiving incentives to encourage participation was statistically less important. Half of the patients reported being better off with DOT than with self-supervised care. CONCLUSIONS: This study confirms the value of patient-focused care among inner-city TB patients.
A modified bacterial artificial chromosome (BAC) vector, pSURF-2, adapted for the selective subcloning of yeast artificial chromosome (YAC) sequences was constructed. DH10B-U, a pyrF derivative of the highly transformable E. coli strain DH10B was also constructed and used for the detection of Ura+ recombinants carrying DNA linked to YAC right arms. The vector's properties were illustrated in two main ways. (i) An intact 25-kb YAC containing a mouse tyrosinase minigene was cloned into pSURF-2. Appropriately spliced tyrosinase RNA was detected by reverse transcription (RT)-PCR in extracts of cells transiently lipofected with the cloned YAC. (ii) Cells expressing human cystic fibrosis transmembrane conductance regulator (CFTR) from an integrated pSURF-2 recombinant containing a cDNA expression cassette were selected using the hygromycin-resistance (HyTK) marker of the vector and characterized by RT-PCR and immunoprecipitation. The unique I-SceI site and HyTK marker of pSURF-2 are designed to facilitate subsequent functional studies of cloned DNA.
In cystic fibrosis (CF), mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene results in defective transepithelial ion transport, leading to life shortening inflammatory lung disease. Before lung studies, we tested the safety and efficacy of gene delivery to the nasal epithelium of CF patients using pCMV-CFTR-DOTAP cationic liposome complex. A single dose of 400 micrograms pCMV-CFTR:2.4 mg DOTAP was administered in a randomised, double-blinded fashion to the nasal epithelium of eight CF patients, with a further eight receiving buffer only. Patients were monitored for signs and symptoms for 2 weeks before treatment and 4 weeks after treatment. Inflammatory cells were quantified in a nasal biopsy taken 3 days after treatment. There was no evidence for excess nasal inflammation, circulating inflammatory markers or other adverse events ascribable to active treatment. Gene transfer and expression were assayed by the polymerase chain reaction. Transgene DNA was detected in seven of the eight treated patients up to 28 days after treatment and vector derived CFTR mRNA in two of the seven patients at +3 and +7 days. Transepithelial ion transport was assayed before and after treatment by nasal potential difference during drug perfusion and by SPQ fluorescence halide ion conductance. Partial, sustained correction of CFTR-related functional changes toward normal values were detected in two treated patients. The level of gene transfer and functional correction were comparable to those reported previously using adenoviral vectors or another DNA-liposome complex, but here were sustained and uncompromised by false positives. These results justify further studies with pCMV-CFTR-DOTAP aimed at treating CF lung disease.
OBJECTIVES: Among the consequences of downsizing and cost containment in hospitals are major changes in the work life of nurses. As hospitals become smaller, patient acuity rises, and the job of nursing becomes more technical and difficult. This article examines the effects of changes in the hospital environment on nurses' job satisfaction and voluntary turnover between 1993 and 1994. METHODS: Data were collected in a longitudinal survey of 736 hospital nurses in one hospital to examine correlates of change in aspects of job satisfaction and predictors of leaving among nurses who terminated in that period. RESULTS: Unadjusted results showed decline in most aspects of satisfaction as measured by Hinshaw and Atwood's and Price and Mueller's scales. Multivariate analysis indicated that the most important determinants of low satisfaction were poor instrumental communication within the organization and too great a workload. Intent to leave was predicted by the perception of little promotional opportunity, high routinization, low decision latitude, and poor communication. Predictors of turnover were fewer years on the job, expressed intent to leave, and not enough time to do the job well. CONCLUSIONS: The authors conclude that although many aspects of job satisfaction are diminished, some factors predicting low satisfaction and turnover may be amenable to change by hospital administrators.
The purposes of this article are (a) to examine cognitive, emotional, and spiritual aspects of hope as reflected in the literature; (b) to describe three clinical approaches that have been used in occupational therapy to engage clients in development of hopes for the future; and (c) to consider practical issues that have been raised by therapists seeking to incorporate development of hopes in their practice. Literature from health care and the social sciences indicates that cognitive, emotional, and spiritual aspects of hope are interwoven in a complex process that evolves over time after major loss. Three alternative clinical strategies for collaborating with clients in developing hopes are reviewed, including a goal-setting and goal-attainment approach, an occupational change approach, and a life history approach. These clinical strategies are illustrated by the stories of an elderly mental health client, an adult rehabilitation client, and an adolescent orthopedic client, which are drawn from research in which the authors have been involved. Discussion of issues involved in incorporating hope work into daily practice is based on the experiences of practicing therapists who participated in a workshop. These include pragmatic issues of documentation and reimbursement of this aspect of practice as well as clinical issues of how to develop hopes among clients who appear hopeless.