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J Douglas

Publications and source records attributed to J Douglas.

At least 19 recordsLinked to original sources
PubMed2007

Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study.

OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.

Adult↗
PubMed2005

Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.

BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.

Abnormalities, Multiple↗
PubMed2005

Partial NSD1 deletions cause 5% of Sotos syndrome and are readily identifiable by multiplex ligation dependent probe amplification.

BACKGROUND: Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions. It is uncertain whether allelic or genetic heterogeneity underlies the residual cases and it has been proposed that other mechanisms, such as 11p15 defects, might be responsible for Sotos cases without NSD1 mutations or 5q35 microdeletions. OBJECTIVE: To develop a multiplex ligation dependent probe amplification (MLPA) assay to screen NSD1 for exonic deletions/duplications. METHODS: Analysis was undertaken of 18 classic Sotos syndrome cases in which NSD1 mutations and 5q35 microdeletions were excluded. Long range polymerase chain reaction (PCR) was used to characterise the mechanism of generation of the partial NSD1 deletions. RESULTS: Eight unique partial NSD1 deletions were identified: exons 1-2 (n = 4), exons 3-5, exons 9-13, exons 19-21, and exon 22. Using long range PCR six of the deletions were confirmed and the precise breakpoints in five cases characterised. This showed that three had arisen through Alu-Alu recombination and two from non-homologous end joining. CONCLUSIONS: MLPA is a robust, inexpensive, simple technique that reliably detects both 5q35 microdeletions and partial NSD1 deletions that together account for approximately 15% of Sotos syndrome.

Base Sequence↗
PubMed2004

The risk factors for depression in first myocardial infarction patients.

BACKGROUND: Depression affects outcome following myocardial infarction but the risk factors for such depression have been little studied. This study considered whether the causes of depression occurring before and after myocardial infarction were similar to those of depression in the general population. METHOD: Consecutive patients admitted to hospital following their first myocardial infarction were interviewed with the Schedule for Clinical Assessment in Neuropsychiatry to detect psychiatric disorders and the Life Events and Difficulties Schedule to assess recent stress. Participants completed the Hospital Anxiety and Depression Scale (HADS) at entry to the study and 1 year later and the risk factors associated with a high score at both times were assessed. RESULTS: Of 314 (88% of eligible) patients who were recruited, 199 (63%) were male and 63 (20%) had depressive disorders. Logistic regression identified the following as independently associated with depressive disorder that had been present for at least I month before the myocardial infarction: younger age, female sex, past psychiatric history, social isolation, having marked non-health difficulties and lack of a close confidant. At follow-up 269/298 (90%) responded; of 189 participants not depressed at first assessment, 39 (21%) became depressed by the 1 year follow-up. Logistic regression identified frequent angina as the only significant predictor of raised HADS scores at 12 months. CONCLUSIONS: Depression developing during the year following myocardial infarction does not have the same risk factors as that which precedes myocardial infarction. Further clarification of the mechanisms linking depression to poor outcome may require separation consideration of pre- and post-myocardial infarction depression, and its risk factors.

Age Factors↗
PubMed2004

Culture-negative Bartonella endocarditis in a patient with renal failure: the value of molecular methods in diagnosis.

Members of the genus Bartonella are increasingly recognised as a cause of culture-negative endocarditis, particularly in those patients with underlying risk factors (e.g., homelessness and alcoholism (B. quintana) or valvulopathy and cat ownership (B. henselae). The aortic and mitral-valves are most commonly involved. Here, a case is reported of culture-negative right-sided endocarditis, without any of the above risk factors, due to Bartonella sp. in a 69-year-old man who presented with acute renal failure. The diagnosis was made using a broad-range 16S rRNA polymerase chain reaction (PCR) technique and direct automated sequencing on a peripheral blood sample, which was subsequently confirmed serologically. A review of the literature on Bartonella endocarditis is also presented. Molecular laboratory methods using peripheral blood or blood cultures may be very useful in the diagnosis of causal agents in culture-negative endocarditis and add further support to the recently inclusion of molecular (PCR) diagnosis, as a major Duke's criterion, for the diagnosis of infective endocarditis.

Acute Kidney Injury↗
PubMed2004

Lack of a close confidant, but not depression, predicts further cardiac events after myocardial infarction.

OBJECTIVE: To assess the role of depression and lack of social support before myocardial infarction (MI) in determining outcome in a large representative sample of patients admitted after MI in the UK. DESIGN: Prospective cohort design. PATIENTS: 1034 consecutive patients were screened 3-4 days after MI. MAIN OUTCOME MEASURES: Mortality and further cardiac events over one year after an MI. RESULTS: At 12 months' follow up mortality and further cardiac events were assessed in 583 of 654 eligible patients (90% response); 140 of 589 for whom baseline data were collected (23.8%) were depressed before their MI. Patients who were depressed before their MI were not more likely to die (mortality 5.2% v 5.0% of non-depressed patients) or suffer further cardiac events (cardiac events rate 20.7% v 20.3% of non-depressed patients). After controlling for demographic factors and severity of MI, the absence of a close confidant predicted further cardiac events (hazard ratio 0.57, p = 0.022). CONCLUSION: Lack of a close confidant but not depression before MI was associated with adverse outcome after MI in this sample. This association may be mediated by unhealthy behaviours and lack of compliance with medical recommendations, but it is also compatible with difficulties in early life leading to heart disease.

Age Factors↗
PubMed2003

Transanal endoscopic excision of rectal adenomas.

Transanal endoscopic microsurgery (TEM) is a minimally invasive surgical technique for performing local excision of rectal lesions in the mid and upper rectum that would otherwise be inaccessible for local excision by the direct transanal approach. In the absence of this approach, low anterior resection would be required, which is major abdominal surgery. The justification for excising adenomas of the colon and rectum is their malignant potential, which correlates with the size of the lesion. This retrospective review examines our experience using TEM for excision of adenomas of the rectum from February 1991 to the present. The decision for using TEM is based on a precise localization of the lesion with particular attention to the upper margin of the lesion and its diameter. A total of 56 adenomas were removed. The average diameter was 4.9 cm (range, 3-8 cm). The average distance from the anal verge was 7.92 cm (range, 5-12 cm). Carcinoma in situ was seen in 7 lesions, and the remaining lesions were benign. Morbidity was minimal, with one conversion to an open procedure for an intraperitoneal perforation that required a low anterior resection. No patient required transfusion and there was no mortality. The hospital stay was short, with half of the patients being discharged the same day. The average cost from July 1996 to December 1999 was 7775 dollars for TEM versus 34,018 dollars for LAR. Subsequent follow-up average was 38.8 months (range, 1-100 months), during which time two patients had recurrence of their adenomas. This was successfully treated with reexcision. In conclusion, TEM is an accurate, safe, and relatively inexpensive technique when compared to low anterior resection. This technique significantly reduces the proportion of adenomas requiring abdominal surgery.

Adenoma↗
PubMed2001

Response to HBV vaccine in relation to vaccine dose and anti-HCV positivity: a New South Wales correctional facilities' study.

Currently, about two-thirds of inmates in NSW correctional facilities have a history of injection drug use, and about half have serological evidence of exposure to hepatitis C virus. The introduction of an accelerated hepatitis B vaccination program (0-1-2 months) in 1998, using a 20 microg/dose vaccine was necessitated by the need to vaccinate eligible inmates in this high-risk environment characterised by rapid client mobility. Since 1999, both 10 and 20 microg doses of vaccine were introduced. We found that sero-response rates were not significantly influenced by HCV antibody status, but were significantly lower in cohorts of inmates vaccinated with the 10 microg dose of vaccine.

Dose-Response Relationship, Immunologic↗
PubMed2001

Protective factors associated with American Indian adolescents' safer sexual patterns.

OBJECTIVES: This paper presents findings from a research partnership with rural American Indian communities to identify protective factors associated with their adolescents' health-related behaviors including 1) delay of sexual debut; 2) not having had intercourse in the past 3 months; 3) birth control use among sexually active adolescents in the past 3 months; 4) condom use in the past 3 months. Our goal was to identify salient characteristics of students and their perceptions of family, school, and friends which could be incorporated or supported in future program planning for adolescents. METHODS: A written survey was administered to 484 Indian students in Grades 6-12 from five rural schools. The survey measured several potential protective factors identified by Problem Behavior Theory, along with self-efficacy and cultural interest and knowledge. Logistic regression assessed the relationship of the protective factors and positive sexual behaviors. RESULTS: Factors significantly associated with abstention from intercourse and/or consistent use of birth control included perceived lower health-risk behavior of friends, higher perceived parental support, higher perceived parental knowledge and monitoring of the adolescent's activities and friends, a higher value on scholastic achievement, higher reported academic performance, and higher self-efficacy for safer sexual behaviors. CONCLUSIONS: This research suggests that Indian adolescents have several protective factors indigenous to their communities which are modifiable. Building on the unique cultural heritage of Indian communities, many of these factors may be addressed through community planned prevention programs.

Adolescent↗
PubMed2001

Recombinant adenovirus expressing adeno-associated virus cap and rep proteins supports production of high-titer recombinant adeno-associated virus.

It has been difficult to produce a chimeric vector containing both Ad and AAV rep and cap, and to grow such chimeric vectors in 293 cells. By recombination in vitro in a bacterial host, we were able to produce recombinant plasmid AdAAV (pAdAAVrep-cap), which could be used to generate recombinant AdAAV (rAdAAVrep-cap) after transfection into 293 cells. A recombinant adenovirus, rAdAAVGFP, in which the green fluorescent protein (GFP) gene is flanked by the AAV terminal repeats cloned into the E1-deleted site of Ad was also generated. Co-infection of rAdAAVrep-cap together with rAdAAVGFP into 293 cells resulted in production of high titers of rAAV expressing GFP. It was noted that the titer of rAdAAVrep-cap was lower than the titer of control AdCMVLacZ. The lower titer of rAdAAvrep-cap was associated with expression of Rep protein. Non-homologous recombination occurs after high passage and results in deletions within the AAV rep genes. These results indicate that (1) rAdAAVrep-cap can be produced; (2) rAdAAVrep-cap + rAdAAVGFP is a convenient and efficient way to transfect 293 cells to grow high titer rAAV; and (3) frozen stock is required to avoid propagation of rep-deleted pAdAAVrep-cap.

Adenoviridae↗
PubMed2001

Guides and wires.

Explore the source record for details and available documents.

Cardiac Catheterization↗
PubMed2001

Pediatric generalists and subspecialists: determinants of career satisfaction.

OBJECTIVES: To evaluate the work life and job satisfaction of pediatric generalists and subspecialists in comparison to each other and to a group of general internists and internal medicine subspecialists. METHODS: Data were collected by survey of a national sample of 5704 general pediatricians, subspecialty pediatricians, general internists, internal medicine subspecialists, and family physicians who were selected randomly from the American Medical Association Masterfile using stratified sampling with disproportionate weighting to ensure ethnic diversity and representation of high managed care areas. Surveys were mailed up to 4 times and contained 150 items that reflected 10 facets of physician job satisfaction as well as an assessment of individual and practice demographic information. This study reports data from all groups except for family medicine. RESULTS: The adjusted response rate was 58% for general pediatricians (n = 590), 67% for specialty pediatricians (n = 345), and 52% (n = 1823) for the entire pool. In comparison with general internists, general pediatricians were more likely to be female (44% vs 24%); to work part time (20% vs 12%); to have lower annual income ($125 679 vs $143 875); and to report significantly higher levels of job, career, and specialty satisfaction on a 5-point scale (3.81 vs 3.52, 3.80 vs 3.55, and 3.76 vs 3.17 respectively). In comparison with internal medicine subspecialists, pediatric subspecialists were more likely to be female (42% vs 22%); to work in academically affiliated settings (35% vs 17%); to have lower incomes ($156 284 vs $192 006); to receive significantly less time for a complete history and physical examination (39 minutes vs 51 minutes); and to report similar levels of job, career, and specialty satisfaction (3.69 vs 3.71, 3.74 vs 3.78, and 3.60 vs 3.47 respectively). Of all 4 physician groups, general pediatricians worked the fewest hours (50/week), spent the greatest percentage of time in the office and the lowest percentage in the hospital (58% and 16%, respectively), saw the lowest percentage of patients with complex medical and complex psychosocial problems (15% and 17%, respectively), and were the least likely to endorse symptoms of burnout or job stress (13% and 18%, respectively). In comparison, pediatric subspecialists worked longer hours (59/week), spent the lowest percentage of time in the office and the greatest percentage of time in the hospital (22% and 44%, respectively), saw a much higher percentage of patients with complex medical and complex psychosocial problems (46% and 25%, respectively), and reported significantly higher levels of burnout and job stress (23% and 26%, respectively). CONCLUSIONS: Despite lower incomes, general pediatricians reported the highest levels of satisfaction and the least job stress of all 4 physician groups, whereas pediatric subspecialists reported levels of stress and burnout that raise significant concerns for the workforce of pediatric subspecialists of the future. Initiatives that improve clinical workload, balance inpatient and outpatient hours, and increase personal time of pediatric subspecialists should be considered.

Burnout, Professional↗
PubMed2001

Assessing the quality of life in children with cystic fibrosis.

Although patients with cystic fibrosis (CF) are experiencing increased longevity, it is unclear that improved quality of life (QoL) accompanies the greater quantity of life. This is especially true of children with CF where the burdens of treatment are substantial. Assessing QoL in such children is difficult, and only one instrument--the Quality of Well-Being (QWB) scale--seems to have been used extensively to assess QoL in children with CF. After thoroughly reviewing the literature, we surveyed the 113 certified CF centers in the United States about QoL assessment. With 84% responding, it was found that only 7 centers are assessing QoL--4 have been using the QWB instrument. Concurrently, we pilot tested the QWB instrument in children being followed longitudinally in the Wisconsin CF Neonatal Screening Project. Our results indicated that QWB scores reflecting QoL decreased as the number of respiratory infections increased, as the number of concurrent medical conditions increased, and as the number of different medications increased. However, we recognized problems with the assessed domains and data interpretation. In fact, the QWB instrument has limited sensitivity and responds more to the extent of physician-determined treatment than to QoL. There is a need for more QoL assessment and better instruments, particularly in young children with CF.

Child↗
PubMed2000

The Andro Project: physiological and hormonal influences of androstenedione supplementation in men 35 to 65 years old participating in a high-intensity resistance training program.

BACKGROUND: Since the passage of The Dietary Supplement Health and Education Act in 1994, there has been a flood of new "dietary" supplements promoting anti-aging benefits such as the enhancement of growth hormone or testosterone levels. Androstenediol and androstenedione are such products. This study's purpose was to elucidate the physiological and hormonal effects of 200 mg/d of oral androstenediol and androstenedione supplementation in men aged 35 to 65 years while participating in a 12-week high-intensity resistance training program. METHODS: Fifty men not consuming any androgenic-enhancing substances and with normal total testosterone levels, prostate-specific antigen, hemoglobin, and hematocrit, and with no sign of cardiovascular or metabolic diseases participated. Subjects were randomly assigned to a placebo, androstenediol (diol), or androstenedione (dione) group using a double-blind study design. Main outcomes included serum sex hormone profile, body composition assessment, muscular strength, and blood lipid profiles. RESULTS: During the 12 weeks of androstenedione or androstenediol use, a significant increase in the aromatization by-products estrone and estradiol was observed in both groups (P =.03). In the dione group, total testosterone levels significantly increased 16% after 1 month of use, but by the end of 12 weeks, they returned to pretreatment levels. This return to baseline levels resulted from increases in aromatization and down-regulation in endogenous testosterone synthesis based on the fact that luteinizing hormone was attenuated 18% to 33% during the treatment period. Neither androstenediol nor androstenedione enhanced the adaptations to resistance training compared with placebo for body composition or muscular strength. However, both androstenediol and androstenedione supplementation adversely affected high-density lipoprotein cholesterol (HDL-C) levels, coronary heart disease risk (representing a 6.5% increase), and each group's respective (low-density lipoprotein cholesterol [LDL-C]/HDL-C)/(apolipoprotein A/apolipoprotein B) lipid ratio (diol: +5.2%; dione: +10.5%; P =.05). In contrast, the placebo group's HDL-C levels increased 5.1%, with a 12.3% decline in the (LDL-C/HDL-C)/(apolipoprotein A/apolipoprotein B) lipid ratio. These negative and positive lipid effects occurred despite no significant alterations in body composition or dietary intakes in the supplemental groups or placebo group, respectively. CONCLUSIONS: Testosterone precursors do not enhance adaptations to resistance training when consumed in dosages recommended by manufacturers. Testosterone precursor supplementation does result in significant increases in estrogen-related compounds, dehydroepiandrosterone sulfate concentrations, down-regulation in testosterone synthesis, and unfavorable alterations in blood lipid and coronary heart disease risk profiles of men aged 35 to 65 years.

Adult↗
PubMed2000

Molecular cloning of a regulatory protein for membrane-bound guanylate cyclase GC-A.

Activation of membrane-bound guanylate cyclase GC-A by atrial natriuretic factor (ANF) may require the involvement of accessory proteins. To identify these postulated proteins, we isolated a 1. 0-kb cDNA clone from a rat brain expression library using a polyclonal antiserum against mastoparan. The 1.0-kb cDNA encodes a protein of 111 amino acids. Expression of this cDNA in COS-7 cells potentiated ANF-stimulated GC-A activity. Therefore, the 1.0-kb gene encodes a guanylate cyclase regulatory protein (GCRP). Fluorescence microscopy studies using the fusion protein of GCRP with green fluorescence protein (GFP) indicated that GCRP was present in the cytosol in PC12 cells, but translocated toward the plasma membrane in the presence of ANF. Coimmunoprecipitation experiments indicate that GCRP associates with GC-A in the presence of ANF. These results suggest that ANF induces the association of GCRP with GC-A and this association contributes to the activation of GC-A.

Amino Acid Sequence↗