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Biomedical subjects

J Barrett

Publications and source records attributed to J Barrett.

At least 37 records · Page 2Linked to original sources

Laboratory evaluation of the molluscicidal properties of some Saudi Arabian euphorbiales against Biomphalaria pfeifferi.

Laboratory studies were conducted to evaluate the molluscicidal properties of three Saudi Arabian Euphorbiales. The results showed that the methanol extract of Euphorbia schimperiana has a high molluscicidal potency. The activity remains stable over a wide range of temperature and pH values, in the presence of organic and inorganic substrates and after exposure of the solutions to ultraviolet radiation.

Aluminum Silicates↗

Proteomic analysis of Fasciola hepatica excretory-secretory products.

This paper describes a global investigation of the components of Fasciola hepatica excretory-secretory (ES) products by a proteomic approach. Despite the absence of a F. hepatica genome sequencing project we have shown that it was possible to identify 29 of the 60 prominent proteins found using two-dimensional gel electrophoresis. As well as cathepsin L proteases, a number of enzymes implicated in parasite protection from the host immune system were also found to be present in relatively large abundance. These included superoxide dismutase, thioredoxin peroxidase, glutathione S-transferases and fatty acid binding proteins, all of which may play a part in the detoxification of reactive oxygen intermediates. Interestingly, ovine superoxide dismutase was the only protein from the host identified on the gel. We suggest that the relative abundance and protective nature of the components of the ES products of this organism play an important role in its survival within the host. The precise identification, to individual NCBI database entries, of a number of glutathione S-transferases and cathepsin Ls from F. hepatica, by peptide mass fingerprinting, was hampered by multi-database submissions of the two protein superfamilies from this organism.

Amino Acid Sequence↗

Proteomic identification of glutathione S-transferases from the model nematode Caenorhabditis elegans.

Glutathione affinity chromatography and two-dimensional electrophoresis (2-DE) were used to purify glutathione binding proteins from Caenorhabditis elegans. All proteins identified after peptide mass fingerprinting using matrix-assisted laser desorption/ionization-time of flight were found to belong to the glutathione S-transferase (GST) superfamily. From the 26 individual spots identified, 12 different GSTs were isolated. Of these, five were found on the gel only once, whilst the remaining seven were represented by 21 separate spots. Most of the GSTs identified were of the nematode specific class, however, three Alpha class GSTs, a Pi and a Sigma class GST were also isolated.

Animals↗

Enhancing patient safety through teamwork training.

The effective reduction of medical errors depends on an environment of safety for patients in both clinically-based and systems-oriented arenas. Formal teamwork training is proposed as a systems approach that will achieve these ends. In a study conducted by Dynamics Research Corporation, weaknesses and error patterns in Emergency Department teamwork were assessed, and a prospective evaluation of a formal teamwork training intervention was conducted. Improvements were obtained in five key teamwork measures, and most importantly, clinical errors were significantly reduced.

Aviation↗

Role of amniotic fluid interphase fluorescence in situ hybridization (FISH) analysis in patient management.

We retrospectively reviewed 309 amniotic fluid interphase fluorescence in situ hybridization (FISH) analyses performed from October 1995 to June 1999 to assess the role of interphase FISH in the management of patients at increased risk for fetal aneuploidies. Gestational age and indications for amniocentesis, clinical interventions after FISH results, as well as interventions after final culture reports were analyzed. There were 244 (79%) normal, 50 (16%) abnormal and 15 (5%) inconclusive FISH results. There were no false-positive or false-negative results, but there were nine (3%) clinically significant chromosomal abnormalities not detectable by FISH. Of the 50 women with abnormal FISH results, 26 (52%) elected to terminate the pregnancy prior to the availability of the standard chromosome analysis. In two of the fetuses with trisomy 21 no abnormalities were reported by ultrasound examination. Our experience indicates that interphase FISH results played an important role in decision making, especially for pregnancies close to 24 weeks' gestation. Standard karyotype analysis is still required for detection of chromosome abnormalities not detectable by interphase FISH techniques and for clarification of unusual or inconclusive FISH results.

Amniotic Fluid↗

Determining which patients require evaluation for blunt cardiac injury following blunt chest trauma.

The objective of this study was to determine prospectively which risk factors require cardiac monitoring for blunt cardiac injury (BCI) following blunt chest trauma. All patients who sustained blunt chest trauma had an electrocardiogram (ECG) on admission to our urban level I trauma center. Those with ST segment changes, dysrhythmias, hemodynamic instability, history of cardiac disease, age > 55 years, or a need for general anesthesia within 24 hours (group 1) were admitted to the intensive care unit (ICU) for 24 hours where they were subjected to serial ECGs, creatinine phosphokinase (CPK) assays, and echocardiography (ECHO). Those with only mechanism for BCI, i.e., none of the above risk factors (group 2), were admitted to a nonmonitored bed and had a follow-up ECG 24 hours later. A series of 315 patients were admitted with blunt chest trauma during a 17-month period; 144 patients were in group 1 and 171 in group 2. Overall, 22 patients were diagnosed as BCI (+BCI), defined as evolving ST segment changes, dysrhythmias, a CPK-MB index of > 2.5, or hemodynamic instability. Of the 18 +BCI patients in group 1, all were symptomatic (i.e., none was included solely for a cardiac history, age, or need for general anesthesia). Six of these patients required treatment for dysrhythmias, hypotension, or pulmonary edema; one of whom died. Four patients with +BCI were in group 2 and had ECG changes at 24 hours; none of these four had any sequelae from their +BCI. None of the ECHOs demonstrated abnormal wall motion. Patients who sustain blunt chest trauma with a normal ECG, normal blood pressure, and no dysrhythmias on admission require no further intervention for BCI. Patients with ST segment changes, dysrhythmias, or hypotension following blunt chest trauma should be monitored for 24 hours, as this subgroup occasionally requires further treatment for complications of BCI. ECHO adds nothing as a screening test.

Adult↗

Long term modulation of the HPA axis by the hippocampus. Behavioral, biochemical and immunological endpoints in rats exposed to chronic mild stress.

Mature rats were given lesions of the hippocampus (HIPPO), subiculum (SUBIC) or fimbria-fornix (FIFO) and then received the mild chronic stressors of food deprivation and isolation housing for ten months prior to testing. Group differences in circadian activity were investigated along with locomotion elicited by amphetamine (AMP 1.0-2.0 mg/kg i.p.) alone, and following the corticosterone (CORT) synthesis inhibitor, metyrapone (MET 10.0-25.0 mg/kg i.p.). Basal levels of plasma CORT, (ng/ml), plasma glucose (GLUC, mmol/l), thymic and splenic wet weights were subsequently determined along with complete blood counts (CBC). In comparison to age matched, unoperated controls, selective SUBIC lesions altered the circadian periodicity of locomotion, while rats with FIFO lesions were spontaneously hyperactive. Both HIPPO and FIFO animals showed significantly higher levels of amphetamine-induced locomotion. In all groups metyrapone significantly enhanced locomotion elicited by amphetamine, probably due to a pharmacokinetic interaction between these drugs. In comparison to controls, animals in the HIPPO group showed significant reductions in plasma glucose levels, decreased thymic wet weights and reductions in lymphocyte numbers, indicating lesion-related immuno-suppression. These findings highlight a functional difference among the effects of these specific hippocampal lesions on neural regulation of the HPA axis, under conditions of chronic mild stress, suggesting that the modulatory influence of the hippocampus on the stress axis is dependent on the neuroanatomical location and total extent of cell loss within this structure. They further suggest that the heightened response to amphetamine occurs independently of any lesion-induced changes in modulation of the HPA axis.

Animals↗

A common class of nematode glutathione S-transferase (GST) revealed by the theoretical proteome of the model organism Caenorhabditis elegans.

The genome verified C. elegans free-living nematode model is a new tool for investigating gene expression in human and animal nematode parasites. There is limited information on designating glutathione S-transferase (GST) to specific classes in lower invertebrates such as nematodes. Following cloning, amino acid sequence alignment, recombinant expression and Western blotting we provide evidence of a new GST class in nematodes or lower invertebrates.

Amino Acid Sequence↗

Thermal hysteresis proteins.

Extreme environments present a wealth of biochemical adaptations. Thermal hysteresis proteins (THPs) have been found in vertebrates, invertebrates, plants, bacteria and fungi and are able to depress the freezing point of water (in the presence of ice crystals) in a non-colligative manner by binding to the surface of nascent ice crystals. The THPs comprise a disparate group of proteins with a variety of tertiary structures and often no common sequence similarities or structural motifs. Different THPs bind to different faces of the ice crystal, and no single mechanism has been proposed to account for THP ice binding affinity and specificity. Experimentally THPs have been used in the cryopreservation of tissues and cells and to induce cold tolerance in freeze susceptible organisms. THPs represent a remarkable example of parallel and convergent evolution with different proteins being adapted for an anti-freeze role.

Adaptation, Biological↗

Electrophysiological analysis of responses of adult females of Brugia pahangi to some chemicals.

Electrophysiological techniques were used to obtain recordings of extracellular electrical activity from the anterior end of live adult females of Brugia pahangi. Stimulation with 100 mM, 10 mM and 1 mM acetylcholine resulted in an increase in spike activity which was concentration dependent, whereas stimulation with phosphate-buffered saline and 0.1 mM acetylcholine gave no increase in activity. The delay in response was not concentration dependent. The action of possible host cues was investigated. Stimulation with heat-inactivated foetal calf serum (IFCS) and 10 mM glutathione gave an increase in spike activity but exposure to 5 mg/dl haemoglobin elicited no response. The response to IFCS was found to be suppressed completely by pre-incubation for 30 min in ivermectin.

Acetylcholine↗

Skinfold caliper and ultrasound assessments of change in the distribution of subcutaneous fat during adolescent pregnancy.

OBJECTIVE: This study compares skinfold caliper and sonographic measurements of the amount and distribution of subcutaneous adipose tissue teenagers gain during pregnancy to test three hypotheses: (1) skinfold caliper and sonographic measurements of subcutaneous adiposity are highly correlated in pregnancy; (2) the extent to which the skinfold caliper heads compact the tissues increases during gestation; and (3) skinfold caliper measurements yield a smaller estimate of the amount of subcutaneous adipose tissue gained during gestation than do sonographic measurements. METHODS: We studied 28 primiparous teenagers at 10.7+/-2.8 and 29.6+/-1.8 weeks gestation. At both study visits subcutaneous adipose tissue thickness was measured at six body sites, first by skinfold caliper and then by ultrasound. Taking the nearly compression-free sonographic measurements as the standard, we quantified the extent to which the skinfold caliper heads compacted the tissues at each measurement site by computing the percentage compression: (mean adipose tissue thickness by ultrasound-(0.5xmean adipose tissue thickness by caliper)/mean adipose tissue thickness by ultrasound)x100. Pearson correlations and paired t-tests were used to compare the skinfold caliper and sonographic measurements. RESULTS: Hypothesis 1 was supported; the skinfold caliper and sonographic measurements were highly correlated at both study visits. Hypothesis 2 was not supported; between study visits caliper-related tissue compression decreased at measurement sites on the trunk and remained the same at measurement sites on the extremities. Hypothesis 3 was also refuted; the skinfold caliper-derived estimate of the amount of subcutaneous adipose tissue gained on the trunk exceeded the corresponding sonographic determination. As anticipated, the skinfold caliper measurements indicated that adipose tissue was stored more rapidly on the trunk than the extremities, but the opposite pattern emerged when the sonographic measurement technique was used. CONCLUSIONS: The results of this study challenge the notion that pregnant women store adipose tissue preferentially on the trunk and suggest that pregnancy-related changes in the regional distribution of maternal body fat based on skinfold caliper measurements should be interpreted cautiously.

Adipose Tissue↗

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↗

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↗

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↗

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↗

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↗

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↗