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J Barrett

Publications and source records attributed to J Barrett.

At least 37 records · Page 2Linked to original sources
PubMed2001

Concerted inhibition of the transcriptional activation functions of the enhancer-binding protein NIFA by the anti-activator NIFL.

The Azotobacter vinelandii NIFL regulatory flavoprotein responds to the redox, energy and nitrogen status of the cell to inhibit transcriptional activation by the sigmaN-dependent enhancer binding protein, NIFA, via the formation of a NIFL-NIFA protein complex. The NIFA protein contains three domains: an N-terminal domain of unknown function; a central catalytic domain required to couple nucleotide hydrolysis to activation of the sigmaN-RNA polymerase holoenzyme; and a C-terminal DNA-binding domain. We report that truncated NIFA proteins that either lack the amino-terminal domain or contain only the isolated central domain remain responsive to inhibition by NIFL but, in contrast to native NIFA, continue to hydrolyse nucleotides when NIFL is present. We also report that NIFL is competent to inhibit the DNA-binding function of NIFA. Taken together, these results suggest that NIFL inhibits NIFA via a concerted mechanism in which DNA binding, catalytic activity and, potentially, interaction with the polymerase are controlled by NIFL in order to prevent transcriptional activation under detrimental environmental conditions.

Azotobacter vinelandii↗
PubMed2001

Allogeneic transplantation using non-myeloablative transplant regimens.

Reduced intensity (non-myeloablative) stem cell transplant (NST) preparative regimens are being increasingly used to exploit the curative potential of allogeneic stem cell transplantation without the morbidity and mortality associated with conventional transplantation. Growing confidence in the power of the allogeneic graft-versus-malignancy (GVM) effect makes such an approach attractive. Lower intensity transplants increase the degree of mixed chimerism, both in T cell and myeloid cell lineages. Currently a variety of NST treatment approaches are being developed and in this chapter their safety profile and the immunological characteristics of the mixed chimeric state are described. Results of NST in specific disease categories are still limited but the NST approach appears to have promise in the treatment of both haematological and non-haematological malignancies because of the benefit of low toxicity coupled with a strong graft-versus-malignancy effect. NST regimens are also being explored in high-risk patients with non-malignant disorders. However, at present, there is insufficient data to determine whether NST should replace standard myeloablative transplants in specific disease groups. With their low toxicity, NST are well placed as platforms for future developments in transplant immunology to avoid GVHD and enhance the allograft effect against malignant diseases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Development and validation of a self-efficacy scale for use in British patients with rheumatoid arthritis (RASE).

OBJECTIVE: Current arthritis self-efficacy scales have attracted some criticism. Therefore, the aim of this study was to develop and validate a measure of self-efficacy for use in British rheumatoid arthritis patients [Rheumatoid Arthritis Self-efficacy (RASE) scale]. METHODS: Phase I: item generation of self-management strategies by rheumatology professionals and patients to create a pilot RASE. Phase II: examination of the internal structure (n=88) using correlation coefficients and principal component analysis (PCA) to create the final RASE. Phase III: reliability in 23 patients. Phase IV: comprehension, construct validity and sensitivity to change in 48 rheumatoid arthritis patients undergoing a self-management programme, using correlation coefficients, PCA and inter-item correlation. RESULTS: Phase I: of 166 self-management items generated, 100 commonly cited items were selected for the pilot RASE. Phase II: using a correlation matrix and PCA, a 28-item RASE was created. Phase III: good 4-week reliability was seen (r=0.889, P<0.001). Phase IV: the final RASE was shown to be independent of mood, disease status and disability and weakly associated with other self-efficacy scales (r=0.313, P<0.05). The RASE was sensitive to change following an education programme (+5.167, P<0.025), and was associated with behaviour initiation (r=0.35, P<0.01). CONCLUSIONS: Careful construction means that the RASE examines beliefs in potential ability to perform tasks, rather than actual ability, performance or outcome expectancy. It shows good face validity and reliability, plus reasonable construct validity and sensitivity. Further studies are needed to support the validation of this new scale.

Adult↗
PubMed2001

Staged reconstruction after gunshot wounds to the abdomen.

Immediate closure of abdominal incisions after exploration and treatment of gunshot wounds is not always feasible or advisable. Significant bowel edema after massive fluid resuscitation might preclude primary closure, whereas any attempt to close under tension might result in complications ranging from wound dehiscence, infection, and necrosis to the abdominal compartment syndrome with abdominal, cardiopulmonary, and renal complications. For these difficult cases, the open technique has been recommended. The abdomen is left open and is closed when the patient's condition permits. When immediate wound approximation is not possible, temporary coverage can be achieved with a mesh, patch, or a split-thickness skin graft and the definitive reconstruction is deferred for a more optimal time. The purpose of this retrospective study is to report the authors' experience with staged abdominal wall reconstruction after gunshot wounds. From 1989 to 1998, 1933 patients underwent exploratory laparotomy for penetrating wounds to the abdomen. Twenty-nine patients in grave condition and with multiple medical problems were comanaged by the Trauma and Plastic Surgery Services at Cook County Hospital with the following protocol: The abdomen was initially left open and exposed viscera were covered with a variety of methods, including a Gore-Tex patch (W. L. Gore and Associates, Inc., Flagstaff, Ariz.). A split-thickness graft was subsequently placed on the granulation tissue over viscera at an average of 14 days after the last laparotomy. These planned ventral hernias were definitively treated at an average of 7 months after the skin grafting procedure, primarily using the components separation technique. In 24 patients, the fascia was closed primarily without tension, while five patients required the use of synthetic mesh to restore fascial continuity. Nine patients underwent closure of a colostomy or repair of fistulas simultaneously with abdominal wall reconstruction. One patient developed a postoperative hernia, two developed superficial wound dehiscence that healed without further surgery, and one required re-exploration for a failed anastomosis after colostomy closure. All but one patient maintained a stable abdominal wall after the reconstruction. The authors concluded that staged abdominal wall reconstruction should be primarily recommended for patients with complex abdominal wounds and a compromised general condition that precludes primary closure. With this treatment protocol, patients can recover faster from their trauma surgery and the risk of perioperative complications can be reduced. After final reconstruction, the continuity, stability, and strength of the abdominal wall are maintained in the vast majority of cases with the use of autogenous tissue and without the need for alloplastic material. With close cooperation between the trauma team and the plastic surgeon and appropriate timing and planning of each stage, the success rate of the technique is high and the incidence of complications limited.

Abdominal Injuries↗
PubMed2001

Management of monoamniotic twin pregnancies: a case series and systematic review of the literature.

OBJECTIVES: To review the experience of the University of Toronto Perinatal Complex, Ontario, Canada concerning antenatally diagnosed monoamniotic twin pregnancies; and to compare our results with cases reported in the literature with respect to antenatal surveillance and perinatal outcome. METHODS: A retrospective chart review of all twin gestations from 1993 to April 2000 was performed. A systematic review of the literature, 1966 to April 2000, of perinatal outcome in monoamniotic twin pregnancies was undertaken. SETTING: All monoamniotic twin gestations at the University of Toronto. RESULTS: Case-series: 25 prenatally diagnosed monoamniotic twin pregnancies were identified. Seven pregnancies were affected by fetal anomalies. One fetus died at 29 weeks. Neonatal complications occurred below 33 weeks of gestational age and were related to immaturity. Systematic review of the literature: 49 studies met our selection criteria and reported 88 cases diagnosed antenatally. Fourteen pregnancies were affected by major congenital anomalies. Twenty fetuses died after 24 weeks of gestation. Neonatal complications varied widely in severity and depended on gestational age at birth. The risk of intrauterine fetal death was 10% at the University of Toronto and 12% in the review of the literature. DISCUSSION: Our experience, the largest so far, suggests that regular fetal surveillance and appropriate steroid administration leads to a good perinatal outcome. The risk of fetal death (10%-12%) is lower than the previously quoted risk of 30%-70%. A careful review of obstetric interventions and further work examining outpatient surveillance of monoamniotic twin pregnancies are needed. The best treatment of monoamniotic twin pregnancies can only be determined by randomised trials.

Adolescent↗
PubMed2001

Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study.

We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C(max)) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 microg/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC(24)) changed to 692, 1,062, 860, and 554 microg x h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of >or=7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n = 43) and in 52 and 13% of the patients in the 7-day evaluable population (n = 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections.

Adult↗
PubMed2001

Protein-protein interactions in the complex between the enhancer binding protein NIFA and the sensor NIFL from Azotobacter vinelandii.

The enhancer binding protein NIFA and the sensor protein NIFL from Azotobacter vinelandii comprise an atypical two-component regulatory system in which signal transduction occurs via complex formation between the two proteins rather than by the phosphotransfer mechanism, which is characteristic of orthodox systems. The inhibitory activity of NIFL towards NIFA is stimulated by ADP binding to the C-terminal domain of NIFL, which bears significant homology to the histidine protein kinase transmitter domains. Adenosine nucleotides, particularly MgADP, also stimulate complex formation between NIFL and NIFA in vitro, allowing isolation of the complex by cochromatography. Using limited proteolysis of the purified proteins, we show here that changes in protease sensitivity of the Q linker regions of both NIFA and NIFL occurred when the complex was formed in the presence of MgADP. The N-terminal domain of NIFA adjacent to the Q linker was also protected by NIFL. Experiments with truncated versions of NIFA demonstrate that the central domain of NIFA is sufficient to cause protection of the Q linker of NIFL, although in this case, stable protein complexes are not detectable by cochromatography.

Adenosine Triphosphate↗
PubMed2001

Analysis of responses of Leidynema appendiculata to acetylcholine using electrophysiological techniques.

The electrophysiological responses of adult females of the insect-parasitic nematode Leidynema appendiculata, to 100 mM, 10 mM, and 1 mM acetylcholine were concentration dependent, with stimulation by 100 mM acetylcholine giving the largest increase in spike activity. By contrast, the delay in response was not concentration dependent. No increase in activity was obtained on stimulation with either 0.1 mM acetylcholine or phosphate-buffered saline. The lack of response to 0.1 mM acetylcholine was confirmed by sequential exposure of L. appendiculata to 0.1 mM acetylcholine and subsequently to 10 mM acetylcholine.

Acetylcholine↗
PubMed2001

Association between hospital and surgeon procedure volume and outcomes of total hip replacement in the United States medicare population.

BACKGROUND: The mortality and complication rates of many surgical procedures are inversely related to hospital procedure volume. The objective of this study was to determine whether the volumes of primary and revision total hip replacements performed at hospitals and by surgeons are associated with rates of mortality and complications. METHODS: We analyzed claims data of Medicare recipients who underwent elective primary total hip replacement (58,521 procedures) or revision total hip replacement (12,956 procedures) between July 1995 and June 1996. We assessed the relationship between surgeon and hospital procedure volume and mortality, dislocation, deep infection, and pulmonary embolus in the first ninety days postoperatively. Analyses were adjusted for age, gender, arthritis diagnosis, comorbid conditions, and income. Analyses of hospital volume were adjusted for surgeon volume, and analyses of surgeon volume were adjusted for hospital volume. RESULTS: Twelve percent of all primary total hip replacements and 49% of all revisions were performed in centers in which ten or fewer of these procedures were carried out in the Medicare population annually. In addition, 52% of the primary total hip replacements and 77% of the revisions were performed by surgeons who carried out ten or fewer of these procedures annually. Patients treated with primary total hip replacement in hospitals in which more than 100 of the procedures were performed per year had a lower risk of death than those treated with primary replacement in hospitals in which ten or fewer procedures were performed per year (mortality rate, 0.7% compared with 1.3%; adjusted odds ratio, 0.58; 95% confidence interval, 0.38, 0.89). Patients treated with primary total hip replacement by surgeons who performed more than fifty of those procedures in Medicare beneficiaries per year had a lower risk of dislocation than those who were treated by surgeons who performed five or fewer of the procedures per year (dislocation rate, 1.5% compared with 4.2%; adjusted odds ratio, 0.49; 95% confidence interval, 0.34, 0.69). Patients who had revision total hip replacement done by surgeons who performed more than ten such procedures per year had a lower rate of mortality than patients who were treated by surgeons who performed three or fewer of the procedures per year (mortality rate, 1.5% compared with 3.1%; adjusted odds ratio, 0.65; 95% confidence interval, 0.44, 0.96). CONCLUSIONS: Patients treated at hospitals and by surgeons with higher annual caseloads of primary and revision total hip replacement had lower rates of mortality and of selected complications. These analyses of Medicare claims are limited by a lack of key clinical information such as operative details and preoperative functional status.

Arthroplasty, Replacement, Hip↗
PubMed2001

Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children.

OBJECTIVE: Oseltamivir (Ro 64-0796) is an ester prodrug of the active metabolite Ro 64-0802 (oseltamivir carboxylate), a potent and selective inhibitor of the neuraminidase enzyme of influenza virus. In this study we report the pharmacokinetics of oseltamivir in healthy children volunteers (study 1) and in children with influenza (study 2). STUDY PARTICIPANTS AND METHODS: In study 1, an open-label, single dose study, serial plasma samples were obtained from a total of 18 healthy children (5 to 18 years) who were grouped by age (n = 6 per group) and received single oral doses of oseltamivir 2 mg/kg. In study 2, a randomised, placebo controlled phase III study in paediatric children (1 to 12 years) presenting with influenza symptoms, 199 pharmacokinetic sparse samples were obtained from 87 patients, and serial samples were obtained from 5 patients. Pooled data were compared with those from adult studies. RESULTS: Children (1 to 12 years) eliminated the active metabolite faster than both adolescents (13 to 18 years) and adults, resulting in lower exposure to the active drug. In these children, oseltamivir 2 mg/kg twice daily resulted in drug exposures within the range associated with tolerability and efficacy in adults administered approximately 1 mg/kg twice daily. Unit doses of oseltamivir 30, 45 and 60mg oral suspension are recommended twice daily in children weighing < or =15 kg (or < or =33 lb, aged 1 to 3 years), > 15 to 23 kg (or >33 to 51 lb, aged 4 to 7 years) and >23 to 40 kg (or >51 to 88 lb, aged 8 to 12 years), respectively. A 75 mg capsule may be a viable dosage formulation in children (e.g. over 8 years of age) who are able to swallow solid dosage forms. CONCLUSIONS: Young children cleared the active metabolite oseltamivir carboxylate at a faster rate than older children and adults. Convenient administration recommendations for the oseltamivir oral suspension in children are possible to maintain drug exposure within the target window.

Acetamides↗
PubMed2001

Linkage and association analysis of candidate genes in rheumatoid arthritis.

OBJECTIVES: To test for linkage and association to rheumatoid arthritis (RA) in multiplex families for polymorphic markers in candidate gene loci. Loci including the cytokine cluster on 5q31.1 and IL10, both previously investigated in RA, were included along with several other genes including ICAM-1, cMYC, the cytokine cluster on 17q11.2 and IL1RA. METHODS: One hundred eighty-five multiplex RA families were genotyped for 11 microsatellite markers close to candidate genes. Markers showing evidence of linkage and/or association to RA were tested in a further cohort of families (n = 99). RESULTS: A single microsatellite marker in the GSTM4 gene showed some evidence of linkage, LOD 1.6 (p = 0.006). However, there was no evidence of excess allele sharing in the second cohort of families tested. There was also evidence of association to RA, using the transmission disequilibrium test for a dinucleotide repeat in the IRF gene in the cytokine cluster on 5q31.1; this was not replicated in a second cohort of families. CONCLUSION: Our results do not provide evidence of a role for these genes in RA susceptibility.

Arthritis, Rheumatoid↗
PubMed2001

A novel interactive electronic protocol review system.

This report describes a new protocol review system which was designed as a Lotus Notes database. This system encompasses all elements of investigator protocol generation, review and approval by the laboratory animal veterinarian and institutional animal care and use committee (IACUC), and notification of approval to personnel responsible for animal ordering. Unique features of the system are interactive dialog between IACUC members and the investigator and confidential protocol discussion among IACUC members. The advantages of the system are multiple: 1. it allows for interactive protocol discussion online; 2. it is an essentially paperless process; 3. inclusion of the outside IACUC member is easily accomplished by using an offsite personal computer and secure remote local-area network access; 4. the time required for protocol generation, review, and approval is streamlined due to the automatic features of the database and the speed of e-mail; and 5. all documentation relating to the protocol and the approval process is archived online.

Animals↗
PubMed2001

Reliability and clinical utility of DSM-IV substance-induced psychiatric disorders in acute psychiatric inpatients.

The goal of his study was to evaluate in 1,951 acute psychiatric inpatients the reliability, construct, convergent, and predictive validity of substance-induced psychiatric syndrome ratings made by clinical attending pschiatrists. The primary admitting condition for each subject was categorically rated by clinical attendings as not, mildly, moderately, or mostly substance-induced at both admission and discharge. Individual substance categories were associated with characteristic demographic, clinical treatment response, and length of stay, findings indicating good construct, predictive validity, and clinical utility. A linear dimensional approach to rating substance-induced syndromes in acute clinical populations may be preferable to the simple dichotomous approach used in DSM-IV.

Acute Disease↗
PubMed2000

A new diagnostic tool for neurocysticercosis is a member of a cestode specific hydrophobic ligand binding protein family.

A protein of unknown function has been identified as a key serological tool for diagnosis of human tapeworm neurocysticercosis, a major worldwide neurological disease. Our own sequence analysis predicts that this protein is a member of a newly identified cestode specific oligomeric hydrophobic ligand binding protein family. In this report, using a rat cestode model, we confirm that homologues of this protein can bind fatty acids and their derivatives, and thus suggest a biological function for this key diagnostic tool.

Acyl Coenzyme A↗
PubMed2000

Treatment of dysthymia and minor depression in primary care: A randomized controlled trial in older adults.

CONTEXT: Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia. OBJECTIVE: To compare the effectiveness of pharmacotherapy and psychotherapy in primary care settings among older persons with minor depression or dysthymia. DESIGN: Randomized, placebo-controlled trial (November 1995-August 1998). SETTING: Four geographically and clinically diverse primary care practices. PARTICIPANTS: A total of 415 primary care patients (mean age, 71 years) with minor depression (n = 204) or dysthymia (n = 211) and a Hamilton Depression Rating Scale (HDRS) score of at least 10 were randomized; 311 (74.9%) completed all study visits. INTERVENTIONS: Patients were randomly assigned to receive paroxetine (n = 137) or placebo (n = 140), starting at 10 mg/d and titrated to a maximum of 40 mg/d, or problem-solving treatment-primary care (PST-PC; n = 138). For the paroxetine and placebo groups, the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring; for the PST-PC group, visits were for psychotherapy. MAIN OUTCOME MEASURES: Depressive symptoms, by the 20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the HDRS; and functional status, by the Medical Outcomes Study Short-Form 36 (SF-36) physical and mental components. RESULTS: Paroxetine patients showed greater (difference in mean [SE] 11-week change in HSCL-D-20 scores, 0.21 [0. 07]; P =.004) symptom resolution than placebo patients. Patients treated with PST-PC did not show more improvement than placebo (difference in mean [SE] change in HSCL-D-20 scores, 0.11 [0.13]; P =.13), but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks (P =.01). For dysthymia, paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high (difference in mean [SE] change in SF-36 mental component scores, 5.8 [2.02]; P =. 01) or intermediate (difference in mean [SE] change in SF-36 mental component scores, 4.4 [1.74]; P =.03). Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo (P>/=.12 for low-, intermediate-, and high-functioning groups). For minor depression, both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning (difference vs placebo in mean [SE] change in SF-36 mental component scores, 4.7 [2.03] for those taking paroxetine; 4.7 [1.96] for the PST-PC treatment; P =.02 vs placebo). CONCLUSIONS: Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression. The benefits of PST-PC were smaller, had slower onset, and were more subject to site differences than those of paroxetine.

Aged↗
PubMed2000

Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo.

Peripheral blood stem cell (PBSC) transplantation is successful in improving engraftment without increasing acute graft-versus-host disease (GVHD), despite much larger numbers of T cells in unmanipulated PBSCs than in bone marrow grafts. In mouse models and retrospective human studies, granulocyte colony-stimulating factor (G-CSF) therapy has been associated with less acute GVHD. We studied the effect of G-CSF on interferon (IFN)-gamma and IL-4 expression in CD4(+) lymphocytes. CD4(+) cells co-cultivated with G-CSF and stimulated with PHA or CD3 monoclonal antibodies showed significant decreases in IFN-gamma and increases in IL-4 expression (n = 13; P <. 01). G-CSF appeared to have a direct effect on CD4(+) cells independent of monocytes present in the culture because purified CD4(+) cells exposed to G-CSF, washed, and cocultivated with untreated monocytes demonstrated similar changes in IFN-gamma and IL-4 expression, whereas untreated CD4(+) cells cocultured with G-CSF-stimulated monocytes behaved as controls. We then studied peripheral blood mononuclear cells (PBMCs) from G-CSF-mobilized PBSC donors. When their PBMCs were cultured with PHA or CD3 monoclonal antibody, the percent of IFN-gamma-expressing cells decreased by a mean of 55% and 42%, respectively, whereas the percent of IL-4-containing cells increased by a mean of 39% and 58%, respectively, following G-CSF stimulation. Increased apoptosis of IFN-gamma-producing CD4(+) cells was not responsible for the shift in TH1/TH2 subsets. G-CSF-R mRNA was present in both CD4(+) and CD8(+) cells. These results suggest that G-CSF decreases IFN-gamma and increases IL-4 production in vitro and in vivo and likely modulates a balance between TH1 and TH2 cells, an effect that may be important in PBSC transplantation.

Antibodies, Monoclonal↗