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Biomedical subjects

T James

Publications and source records attributed to T James.

At least 37 records · Page 2Linked to original sources

Attentional reactions to an MI: the impact of mood state, worry, and coping style.

This study investigated the possible development of an attentional bias to cardiac-related words in subjects who recently experienced a myocardial infarction (MI). It was hypothesized that cardiac-related stimuli would have attention-capturing characteristics for post-MI subjects, and this bias would be moderated by level of anxiety, degree of cardiac-related worry, and the subject's coping style. Post-MI subjects (n = 33) and matched controls (n = 31) participated in an attentional search task. The post-MI subjects failed to show the predicted group increases in attention allocated to cardiac stimuli, but a difference between groups still occurred as the control group exhibited directed inattention to cardiac stimuli. Subsequent analysis indicated those post-MI subjects who did evince an attentional bias toward cardiac stimuli had higher monitoring scores on a self-report measure of coping style. Level of emotional distress and cardiac-related worry failed to predict attentional bias for the post-MI subjects.

Adaptation, Psychological↗

Glycaemic control and familial factors determine hyperlipidaemia in early childhood diabetes. Oxford Regional Prospective Study of Childhood Diabetes.

AIMS: To determine whether abnormal lipid levels in children with Type 1 diabetes mellitus are the result of poor metabolic control or may in part be determined by genetic factors. METHODS: Non-fasting lipid levels were measured in 141 children with Type 1 diabetes (age range 7.7-19 years) 3 years after diagnosis, and in 192 of their parents. Glycosylated haemoglobin and the urinary albumin-creatinine ratio (three urine samples) were estimated in each child annually. RESULTS: The children had a mean total cholesterol of 4.46 +/- 1.25 mmol/l (+/- SD) and a median triacylglycerol of 1.18 mmol/l (range 0.32-4.7). A total of 15.3% of the population had a total cholesterol > 5.2 mmol/l and 17.9% had a triacylglycerol > 1.7 mmol/l; in 5.6% both total cholesterol and triacylglycerol were greater than these cut-off points. Total cholesterol, triacylglycerol and very low density lipoprotein-cholesterol were significantly correlated to glycaemic control. However, total cholesterol was also significantly related to parental total cholesterol either as analysed separately or as mean parental total cholesterol (r = 0.37, P = 0.0001). In stepwise multiple regression analysis both mean parental total cholesterol (P = 0.001) and HbA1c (P = 0.015) were significant determinants of the child's total cholesterol. The children studied were being followed prospectively for the development of microalbuminuria and there was a weak association across tertiles of total cholesterol, linking higher levels to the development of microalbuminuria (P < 0.05). CONCLUSIONS: We conclude that both glycaemic control and familial factors may be important determinants of lipid levels in young people with diabetes. Both may contribute to the subsequent risk of cardiovascular disease and possibly the development of incipient diabetic nephropathy.

Adolescent↗

Sabbatical programs and the status of academic emergency medicine: a survey.

OBJECTIVES: The Society for Academic Emergency Medicine (SAEM) commissioned a survey in 1998 to describe sabbatical programs, academic rank, and tenure, and to shed light on factors affecting the continuum of faculty development, as a context for evaluating the potential importance of emergency medicine (EM) sabbatical programs. METHODS: The chairs of 120 EM residency programs were surveyed. RESULTS: The response rate was 90%. Of 108 responses, 44 were academic EM departments (AEMDs); ten were their affiliates. The setting was urban for 82%; 37% were publicly funded and 58% privately. AEMDs were more likely to have a tenure track and eligibility for a sabbatical program, but not more likely to use a sabbatical program. Among 2,042 ranked EM faculty, there were 121 professors and 346 associate professors. Mean sabbatical length was six months, provided at full pay requiring a mean of 5.7 years of employment. Among 39 programs reporting eligibility for an EM sabbatical, requirements included: tenure (43%), academic rank of associate professor (78%), an application with multiple approval levels (92%), and a formal report (75%). Thirteen EM programs used sabbaticals; only 40 faculty members altogether (9% of senior faculty) have taken sabbaticals. The mean value of sabbaticals (rated by users on a scale of 1 to 10) was 6.8. Reduced funding, lack of departmental status, difficulty retaining faculty, Health Care Financing Administration (HCFA) regulations, graduate medical education (GME) cutbacks, and no release time were identified as challenges for emergency physicians (EPs) wishing to participate in sabbaticals. Strategies proposed to overcome these obstacles include quality customer service, streamlined operations, outside contracts, computerization, hiring individuals with PhDs, collaboration, political activity, and faculty development. CONCLUSIONS: A sabbatical can be beneficial for individuals and their institutions, but presently EPs have not been able to maximize use of available opportunities. Some obstacles to successful participation of EM in sabbatical programs might be overcome with creative strategies and the active support of professional academic organizations.

Career Mobility↗

Ethical considerations in qualitative research with vulnerable groups: exploring lesbians' and gay men's experiences of health care--a personal perspective.

It is rare to find honest accounts of the difficulties and dilemmas encountered when conducting sensitive research with vulnerable research populations. This account explores some of the ethical issues raised by a qualitative interview study with lesbians and gay men about their experiences of nursing care. There is tension between the moral duty to conduct research with vulnerable and stigmatized groups in order to improve care, and the inevitable lack of resources that go with such a venture. This increases the risk of harm during the process of research. The risk of harm to both the researchers and the researched is explored and the need for a support structure for both groups is raised. There is a pressing need to develop further understanding about the ways in which the dissemination of research can potentially harm already vulnerable research populations.

Attitude to Health↗

Effects of dietary nitrogen manipulation on ammonia volatilization from manure from Holstein heifers.

Decomposition of livestock manure produces gaseous ammonia. Dietary manipulation is one means to reduce N in manure and ammonia volatilization. The effects of dietary crude protein concentration on N intake, N and urinary urea-N excretion, and ammonia volatilization were measured. Eight Holstein heifers (body weight = 260 to 488 kg) were fed a total mixed ration containing either 9.6 or 11.0% crude protein in a crossover design. Oatlage and concentrate were fed at 77:23 (dry matter basis), and soybean meal was used to alter total dietary crude protein. Seven-day adjustment periods preceded 5-d collection periods. Indwelling urinary catheters were inserted 2 d prior to the collection periods. Daily feces and acidified urine were collected, stirred, and subsampled for total Kjeldahl N, urinary urea N, dry matter, P, K, and ash. Urine collection tubes were split during period 2 to allow for collection of unacidified samples for urea N and total N determinations. Unacidified urine and fecal samples were combined (1:1.3) for collection of volatilized ammonia. Remaining slurries were extracted for total and urea N. Increased dietary crude protein concentration increased N intake, N excretion, urea-N excretion, and N excreted in the urine by the heifers. Dietary manipulation of N intake by reduction of 14.0% (dry matter basis) resulted in a 28.1% decrease in ammonia emission and decreases in the urea N, total N, and percentage N excreted in the urine of 29.6, 19.8, and 7.4%, respectively. Ammonia volatilization was dependent on N quantity and form in the urine.

Ammonia↗

Gene-enhanced tissue engineering: applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene.

Periosteum has cell populations, including osteoprogenitor and chondroprogenitor cells, that can be grown in cell culture and form both bone and cartilage under appropriate conditions. The authors have shown previously that cultured periosteal cells can be used in the tissue engineering of bone, and they demonstrated substantial bone formation in a rabbit cranial defect model. In the current study, principles of tissue engineering were combined with principles of gene therapy to produce cultured periosteal cells transduced retrovirally with the bone morphogenetic protein 7 (BMP-7) gene to be used in the treatment of bone defects. Human BMP-7 complementary deoxyribonucleic acid was generated from a cell line using reverse transcription polymerase chain reaction and cloned into a retroviral vector plasmid. Retroviral vector particles were then used to transduce New Zealand White rabbit periosteal cells. Transduced periosteal cells demonstrated substantial production of both BMP-7 messenger ribonucleic acid by Northern blot analysis and BMP-7 protein by enzyme-linked immunosorbent assay. These cells were then seeded into polyglycolic acid (PGA) matrices and used to repair critical-size rabbit cranial defects. At 12 weeks, defect sites repaired with BMP-7-transduced periosteal cells/PGA had significantly increased radiographic and histological evidence of bone repair compared with those defect sites repaired with negative control-transduced cells/PGA, nontransduced cells/PGA, PGA alone, or unrepaired defects. Thus, this study demonstrates successfully a tissue engineering approach to bone repair using genetically modified cells.

Animals↗

New inhibitors of calpain prevent degradation of cytoskeletal and myelin proteins in spinal cord in vitro.

We have determined the effects of the calpain inhibitors AK275 and AK295 upon purified m-calpain and calcium-mediated degradation of neurofilament protein (NFP) in rat spinal cord in vitro. After incubation, the soluble radioactivity and/or extent of myelin basic protein (MBP) or NFP degradation was determined. Fifty percent of caseinolytic activity was inhibited by both inhibitors at 0.6 microM concentration, while more than 90% inhibition was seen at 1.6 microM. In contrast, 37% and 64% inhibition of MBP degradation was seen with AK295 and AK275, respectively, at 10 microM concentration. The extent of NFP degradation in spinal cord was quantified from immunoblot enhanced chemiluminescence. The calcium-mediated breakdown of NFP was inhibited by both AK275 and AK295, and the inhibition was dose-dependent. A 50% inhibition of NFP degradation was seen with AK295 at 10 microM and was almost completely inhibited at 25-50 microM. AK295 was slightly more potent than AK275. These studies suggest that these potent calpain inhibitors may be used therapeutically to provide neuroprotection in vivo in experimental central nervous system trauma and ischemia.

Animals↗

A model for the fluid motion of vitreous humour of the human eye during saccadic movement.

During saccadic motion the eyewall moves in a manner similar to a sinusoid or at least can be represented by a sine Fourier series. Motion of the vitreous is induced by the saccade and the vitreo-retinal interface is subjected to a time-dependent shear. This force may be a significant factor for retinal tearing in the neighbourhood of small retinal holes or tears. An analytical viscoelastic model and a numerical, Newtonian model of the motion of the vitreous are presented and compared. Under sinusoidal boundary motion the analytical model shows that a viscous wave propagates inward toward the axis of rotation and the characteristic length of this wave is a function of the Womersley number. The numerical solution indicates that the vitreous moves similarly to the analytical result with small secondary motion; however, this motion allows complete recirculation of the vitreous over large timescales. Excellent agreement is found between the analytical and numerical models. The time-dependent fluid shear is evaluated and from the analytical solution the maximum value of this is found to be proportional to R0 square root of v(omega)3, where R0 is the eye radius, v the modified complex viscosity and omega the sinusoidal frequency. This indicates that myopes have a larger shear force exerted on them by virtue of the larger eye size. Further work is directed toward a model which links the stress found in the sclera to that exerted on the vitreo-retinal interface by the vitreous fluid motion.

Biophysical Phenomena↗

Time-dependent stress and displacement of the eye wall tissue of the human eye.

Myopia or short sightedness, is the most important predisposing factor to retinal detachment. The relative risk of detachment rises with increasing myopia. The model characterizes that because the severity of myopia increases with the axial length (antero-posterior diameter) of the eyeball, the relative risk of retinal detachment rises with increasing eye size. We present a mathematical model of the time-dependent shear stress force that occurs in the thin eye wall shell supporting the vitreous humour inside the eye globe during the acceleration and deceleration phases of saccadic eye movement. Results show that the shear force increases as the thickness of the eye wall decreases. It is common for myopes to have thinner eye wall tissue than emmetropes. In addition, if account is taken of the increased force required to provide normal saccadic movement of myopic (larger) eyes, then the shear force is up to seven times greater than that experienced for emmetropes.

Biomechanical Phenomena↗

Methodological issues conducting sensitive research on lesbian and gay men's experience of nursing care.

This paper is a methodological discussion on a qualitative research project which involved interviewing lesbians and gay men about their experiences of nursing care. The research project arose primarily because most of the knowledge available on the subject was based on hearsay and anecdote. It is worthy of note that those who felt there was an issue to be addressed, as well as the bearers of anecdote, were by and large what would be termed 'insiders' in ethnographic research, and zealots with an axe to grind in less academic circles. It is the nature of this "insider' status which is of interest throughout the research process of what was and remains a sensitive research topic. 'Insider' status can reduce many of the problems associated with conducting sensitive research in terms of access, rapport with subjects, ethical concerns, and stigma contagion, but by the same token lays researchers open to the charge of bias thought to be inherent in going native, or rather in this case being native. However, there are some problems associated with 'insider' status as well and this paper offers a discussion of the methodological problems we have encountered in relation to this, as well as more general methodological issues when conducting research considered to be sensitive. Ethical dilemmas also arose during the research when lesbian and gay patients who were currently receiving hospital care contacted the researchers directly because they felt threatened by nursing and medical staff. The paper is an attempt to describe some fairly conscious strategies to use the research team's 'insider' status for methodological reasons and to explain the ethical position we took when we felt compromised.

Attitude of Health Personnel↗

AS-1 red cells for neonatal transfusions: a randomized trial assessing donor exposure and safety.

BACKGROUND: Despite recent optimism about the use of erythropoietin therapy to treat the anemia of prematurity, very-low-birth-weight infants who are severely ill receive multiple red cell (RBC) transfusions. Many physicians transfuse relatively fresh RBCs to newborn infants, exposing them to multiple donors and possibly increasing their risk of acquiring transfusion-transmitted infections. STUDY DESIGN AND METHODS: A randomized, single-blind clinical trial was conducted to determine, as the primary endpoint, whether RBCs collected from one dedicated donor and stored for < or = 42 days in AS-1 storage media could safely supply all small-volume RBC transfusions (15 mL/kg/dose) needed by very-low-birth-weight infants (0.6-1.3 kg) during the first 84 days of life. Secondary endpoints were the assessment of the possible adverse clinical and biochemical effects of transfusing AS-1 RBCs stored for < or = 42 days. Control infants received identical nursery care, except they received fresh RBCs stored < or = 7 days in CPDA-1. RESULTS: Infants transfused with AS-1 RBCs were exposed to a mean of 1.6 donors,-compared with an exposure to 3.7 donors for infants given CPDA-1 RBCs (p < 0.05). Neither clinical transfusion reactions nor the results of multiple laboratory tests were significantly different in infants who received slow transfusions (15 mL/kg) of AS-1 RBCs stored for < or = 42 days and in infants who received the same volume of CPDA-1 RBCs stored < or = 7 days. CONCLUSION: AS-1 RBCs, usually from only one dedicated donor, can safely supply all RBCs needed by most very-low-birth-weight infants-a practice that decreases donor exposure and likely increases transfusion safety.

Adenine↗

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗

Inhibition of bronchospasm and ozone-induced airway hyperresponsiveness in the guinea-pig by CDP840, a novel phosphodiesterase type 4 inhibitor.

1. The activity of CDP840, a novel, potent and selective cyclic nucleotide phosphodiesterase type 4 (PDE 4) inhibitor, was evaluated in guinea-pig models (in vitro and in vivo) of bronchospasm, ozone-induced airway hyperresponsiveness (AHR) and non-cholinergic bronchoconstriction. Comparisons were made with (i) other PDE 4 inhibitors: CT1731 (S-enantiomer of CDP840), rolipram, RP73401 and (ii) the clinically used agents salbutamol and theophylline. 2. CDP840 relaxed isolated trachea, under basal tone (EC50 4.5 +/- 1.1 microM) being 17 fold less potent than rolipram (EC50 0.26 +/- 0.13 microM) but attaining the same Emax (83 +/- 6% of the response to 300 microM papaverine). 3. CDP840 relaxed tracheae pre-contracted with carbachol (IC25 39 +/- 9 microM) and histamine (IC25 4 +/- 1 microM) producing monophasic curves. Stereoselectivity was not observed with CT1731 against either carbachol (IC25 33 +/- 11 microM) or histamine (IC25 17 +/- 10 microM). Aminophylline was 1.6 fold (carbachol) and 11 fold (histamine) less potent than CDP840. Rolipram and RP73401 produced tri-phasic relaxation curves but were of similar potency (at the IC25 level) to CDP840 against carbachol (rolipram 18 +/- 5 microM, RP73401 39 +/- 1 microM) whereas against histamine they were approximately 20 fold more potent (rolipram 0.2 +/- 0.1 microM, RP73401 0.2 +/- 0.1 microM). In producing > 30% (carbachol) and > 60% (histamine) relaxation these inhibitors had similar potency and were poor compared to salbutamol. 4. Pre-incubation with CDP840 (10 microM) did not antagonize histamine-induced contraction of isolated trachea; however, it did cause a slight potentiation of the subsequent relaxation to salbutamol (IC50 23 +/- 1 to 15 +/- 2 nM). 5. Pretreatment (1 h) with either CDP840 (1 mg kg-1, i.p. or 3 mg kg-1, i.v.) or rolipram (1 mg kg-1, i.p.) did not bronchodilate or antagonize bronchospasm due to inhaled histamine in anaesthetized, ventilated guinea-pigs. Salbutamol (1 mg kg-1, i.p.) did not bronchodilate but caused a parallel 7 fold rightward shift in the histamine dose-response curve. 6. Stimulation of the vagus nerve in the presence of atropine resulted in a frequency-related bronchoconstriction. CDP840 and rolipram (i.v.) inhibited the response being approximately equipotent (EC50 approximately 10 micrograms kg-1). Neither drug inhibited bronchospasm to inhaled substance P. 7. CDP840 (1-10 micrograms kg-1 i.p.) dose relatedly inhibited ozone-induced bronchoconstriction. CT1731 (1 mg kg-1), rolipram (1 mg kg-1), RP73401 (10 micrograms kg-1) and aminophylline (10 mg kg-1) had no effect. Ozone-induced AHR to inhaled histamine was inhibited by CDP840 in a dose-related manner, 10 micrograms kg-1 abolishing the AHR. This effect was stereoselective as CT1731 was approximately 30 fold less potent than CDP840. Rolipram was approximately 100 fold less potent and RP73401 and aminophylline had no effect. CDP840 was orally active being approximately 10 fold less potent compared to i.p. administration. 8. CDP840 is a poor spasmolytic and anti-spasmogenic agent in response to exogenous mediators; however, it potently inhibits vagally mediated non-cholinergic bronchoconstriction and ozone-induced AHR to histamine. It is possible that regulation of cyclic AMP by PDE 4 contributes to neuronal sensitivity in the airways. Furthermore, CDP840 may suppress AHR without being an overt bronchodilator. Such a profile of activity may have therapeutic benefit in airways diseases such as asthma.

Analysis of Variance↗

Snake envenomation in cats and its detection by rapid immunoassay.

OBJECTIVE: To determine the usefulness of a snake venom detection kit (SVDK) in the management of envenomed cats. DESIGN: A clinical study. ANIMALS: Twenty-two cats were investigated. PROCEDURE: Cats injected subcutaneously with approximately 0.25 or 1.0 lethal dose (LD) of tiger snake venom or 1 or 4 LD of brown snake venom were observed for clinical symptoms of envenomation at intervals over the ensuring 24 to 48 hours(h). Blood and urine samples were taken at regular intervals and assayed in a quantitative laboratory assay for snake venoms. Selected samples were assayed in parallel in a rapid, semi-quantitative SVDK. RESULTS: The studies showed that it was important to estimate the elapsed time from envenomation to presentation. If this time was less than 8 h, blood was the most appropriate sample and a negative result should exclude serious envenomation. If the elapsed time exceeded 8 h, it was essential that urine be sampled. Venom levels in urine were high at 8 h and approached the level of test sensitivity over 24 to 48 h; however by this time clinical signs were obvious in endangered cats. CONCLUSIONS: Careful use of the SVDK is a valuable aid in the management of a potentially envenomed cat.

Animals↗