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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 307 records · Page 17Linked to original sources
PubMed1995

Hyperinsulinaemia of hypertriglyceridaemia: a reappraisal.

The peripheral hyperinsulinaemia of hypertriglyceridaemic subjects has only been defined using insulin immunoassays in which proinsulin and proinsulin fragments cross-react. Relative contributions of pancreatic secretion and hepatic extraction of insulin to this hyperinsulinaemia have not been studied. We, therefore, reassessed the hyperinsulinaemia of hypertriglyceridaemia by measuring fasting plasma concentrations of intact proinsulin, glucose, insulin, and C-peptide in 24 hypertriglyceridaemic subjects with normal glucose tolerance (n = 14) and with impaired glucose intolerance (n = 10) and in normal subjects (n = 14). Hypertriglyceridaemic subjects had higher (p < 0.01) fasting concentrations of insulin and C-peptide and greater (p < 0.01) fasting insulin: C-peptide molar ratios than in control subjects. Fasting intact proinsulin concentrations were similar in hypertriglyceridaemic subjects with normal glucose tolerance and control subjects but these were lower (p < 0.01) than in hypertriglyceridaemic subjects with impaired glucose tolerance. These results suggest that the fasting peripheral hyperinsulinaemia of hypertriglyceridaemic subjects is due to increased pancreatic secretion and reduced hepatic fractional extraction of insulin. The peripheral hyperinsulinaemia of hypertriglyceridaemia appears to reflect peripheral insulin resistance and is not attributable to elevated proinsulin concentrations which are characteristic of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus.

Adult↗
PubMed1995

Autobiographical memory and chronic pain.

The influence of chronic pain on the recall of autobiographical memories of pain and non-pain events was examined. Eleven chronic pain patients and 11 age- and sex-matched control subjects retrieved autobiographical memories to neutral and pain-related cue words. Patients and controls retrieved equal numbers of memories, but pain subjects retrieved more memories incorporating elements of physical pain. Analysis of the content of these memories revealed that patients and controls recalled equal numbers of memories of themselves and other people in acute pain and that the difference observed was attributable to the pain patients recalling memories of themselves in chronic pain. Memories of pain were recalled significantly faster than non-pain memories. The results are discussed with reference to the possible biasing effects of pain state on memory and the schematic processing of pain memories.

Adolescent↗
PubMed1995

A controlled double blind study of azathioprine in the management of Crohn's disease.

While immunosuppressive agents are used widely in the management of Crohn's disease, their efficacy has not been well established in randomised controlled trials. This study was designed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks. It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn's disease over a period of 15 months. Sixty three patients with active Crohn's disease were treated with a 12 weeks diminishing dose of prednisolone and at the same time entered into a randomised, double blind 15 month trial of either azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were compared at 12 weeks and at 15 months. There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission (42% receiving azathioprine v 7% receiving placebo), p = 0.001. Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial (p = 0.02). There were significantly greater decreases over the trial period in the median erythrocyte sedimentation rate, C reactive protein, and leucocyte count in the azathioprine group. There were no cases of severe bone marrow suppression or clinical pancreatitis. In conclusion, azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn's disease.

Adolescent↗
PubMed1995

An assessment of the intrauterine sound intensity level during obstetric echo-planar magnetic resonance imaging.

In order to assess the sound level experienced by the fetal ear during obstetric magnetic resonance imaging, a fluid filled stomach was used as an experimental model of the gravid uterus. A better than 30 dB attenuation in intensity was recorded across the frequency band of interest for all patient orientations. This was enough to reduce acoustic sound pressure from a level close to the instantaneous damage threshold (120 dB), to an acceptable level (< 90 dB). Direct mechanical coupling through the patient table was also shown to increase uterine sound pressure levels by as much as 10 dB. Much higher peak pressures could be obtained by tapping of abdomen with the fingers.

Acoustics↗
PubMed1995

Rates of tibial osteotomies in Canada and the United States.

This study determined the temporal trends and factors associated with the rates of performance of tibial osteotomies from 1985 to 1990 in Ontario, Canada and the United States. The Health Care Financing Administration, Ontario Health Insurance Plan, and National Hospital Discharge Survey databases were used to determine the number of osteotomies from 1985 to 1990. Osteotomy rates decreased in both countries approximately by 11% to 14% per year in patients 65 years and older and by 3% to 4% per year in patients younger than 65 years. Men received twice as many osteotomies as women in both countries. In the United States, the average rate of tibial osteotomies was 2 to 3 times lower than in Ontario.

Age Factors↗
PubMed1995

Recommended guidelines for uniform reporting of pediatric advanced life support: the pediatric Utstein style. A statement for healthcare professionals from a task force of the American Academy of Pediatrics, the American Heart Association, and the European Resuscitation Council.

This consensus document is an attempt to provide an organized method of reporting pediatric ALS data in out-of-hospital, emergency department, and in-hospital settings. For this methodology to gain wide acceptance, the task force encourages development of a common data set for both adult and pediatric ALS interventions. In addition, every effort should be made to ensure that consistent definitions are used in all age groups. As health care changes, we will all be challenged to document the effectiveness of what we currently do and show how new interventions or methods of treatment improve outcome and/or reduce cost. Only through collaborative research will we obtain the necessary data. For these reasons, and to improve the quality of care and patient outcomes, it is the hope of the task force that clinical researchers will follow the recommendations in this document. It is recognized that further refinements of this statement will be needed; these recommendations will improve only when researchers, clinicians, and EMS personnel use them, work with them, and modify them. Suggestions, emendations, and other comments aimed at improving the reporting of pediatric resuscitation should be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital of The King's Daughter, Division of Critical Care Medicine, 601 Children's Lane, Norfolk, VA 23507.

Child↗
PubMed1995

Can patients become empowered?

Organisations can limit freedom of choice by enforcing conformity to policies and procedures. In-depth analysis of the concept of empowerment is needed to encourage its use in nursing.

Attitude of Health Personnel↗
PubMed1995

Comparison of a generic and a disease-specific measure of pain and physical function after knee replacement surgery.

Generic and disease-specific health status instruments are commonly used to assess patients' outcomes. The hypothesis that they measure distinct but complementary aspects of patients' quality of life was tested using a sample of patients aged 67 to 99 years who had undergone knee replacement surgery 2 to 7 years previously. Patients' scores on a generic health-related quality-of-life (HRQOL) measure, the SF-36, were compared to those of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; the WOMAC was developed specifically for patients with lower extremity arthritis, whereas the SF-36 is aimed at all conditions. A stratified sample of 1,750 Medicare beneficiaries was surveyed and an overall response rate of 80.3% achieved, resulting in 1,193 usable surveys (after adjustment for ineligible, incapacitated, and deceased individuals). The distribution of scores on the three dimensions common to both instruments (i.e., pain, physical function, and overall score) showed consistently higher scores on the WOMAC, on a scale of 0 (worst) to 100 (best), than on the SF-36, indicating less disability from arthritis than from other conditions after knee surgery in this elderly population. Statistically significant differences in the number of people with perfectly healthy scores were detected between the instruments; with regard to pain, 32.2% of the sample reported no pain due to arthritis on the WOMAC, compared with only 13.6% reporting no pain due to any conditions on the SF-36. The figures for physical function and overall score were 9.6% versus 1.4%, and 6.9% versus 0.2%, respectively. Examination for discriminant validity showed that the scores on the two scales followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. The results of this study support the inclusion of both a generic and a disease-specific HRQOL measure to assess patient outcomes fully.

Aged↗
PubMed1995

Pulmonary capillaries are smaller in the centre than in the periphery of the guinea-pig lung lobule: possible contributory mechanism for the centrilobular location of emphysema?

We used scanning electron microscopic morphometry of microvascular corrosion casts to compare the capillary structure in the centre and periphery of the lung lobule in the guinea-pig. Capillaries in the centre of the lobule had a lesser diameter than in the periphery (8.6 +/- 1.6 vs 10.4 +/- 1.9 microns respectively, P < 0.001). The polygonal capillary rings differed in structure between the centre and periphery of the lobule, although the number of branches remained constant. Capillary density in the centre of the lung (0.71 +/- 0.05) was significantly less than in its periphery (0.78 +/- 0.06, P < 0.001). We conclude that the capillary structure of the centre of the lung lobule is markedly different from that seen in the periphery. The smaller capillary diameter seen in the centre might be important in trapping polymorphonuclear leucocytes that lose the ability to deform after contact with cigarette smoke components; such an effect could explain why cigarette smoke induced emphysema tends to involve the centre of the lung lobule.

Animals↗
PubMed1995

Effects of cigarette smoke and asbestos on airway, vascular and mesothelial cell proliferation.

In order to determine whether exposure to both cigarette smoke and asbestos leads to enhanced cell proliferation, and whether pleura cell proliferation reflects the presence of fibres at or near the pleura, rats were exposed to air (control), daily cigarette smoke, a single intratracheal instillation of amosite asbestos, or a combination of smoke and asbestos. Dividing cells were labelled with bromodeoxyuridine (BrdU) and animals were sacrificed at 1, 2, 7 or 14 days. Both cigarette smoke and asbestos produced increases in the labelling index of small airway wall, epithelial cells and pulmonary artery cells. In the small airways there was a brief marked positive synergistic interaction between these two agents, but synergism was not seen in the vessels. Cigarette smoke did not increase the labelling of mesothelial or submesothelial cells, whereas asbestos caused a persisting increase in mesothelial cell labelling. There was no correlation between the number of BrdU labelled mesothelial or submesothelial cells and the number of fibres touching the pleura, or located within 180 microns of the pleura. We conclude that the combination of cigarette smoke and asbestos exposure produces a complex set of interactions and has the potential to markedly increase cell proliferation in the parenchyma, an effect that may be important in both fibrogenesis and carcinogenesis. In contrast to the diminishing effects over time of a single dose of asbestos on cell proliferation in the small airways and vessels, the same dose of asbestos leads to sustained mesothelial cell proliferation. However, the latter process does not correlate with local accumulation of asbestos fibres.

Animals↗
PubMed1995

Phase I study of etoposide phosphate (etopophos) as a 30-minute infusion on days 1, 3, and 5.

Etoposide phophate is a phosphate ester prodrug of etoposide designed to improve the pharmaceutical characteristics of the parent compound. A Phase I dose-escalating study of etoposide phosphate was conducted concurrently at two institutions to determine its toxicity, pharmacokinetics, and maximum tolerated dose. Etoposide phosphate was administered i.v. for 30 min on days 1, 3, and 5 every 21 days or on recovery from toxicity. Cohorts of at least three patients received etoposide phosphate at dose levels from 50 mg/m2 to 150 mg/m2 expressed as molar equivalents of etoposide. Blood and urine samples were obtained from all patients during the first cycle of treatment and the concentrations of etoposide phosphate and etoposide were measured. Thirty-nine patients with documented cancers received a total of 75 cycles of etoposide phosphate. The dose-limiting toxicity was myelosuppression which occurred at the 150-mg/m2 etoposide equivalent dose. Etoposide phosphate was rapidly and extensively converted to etoposide. No measurable etoposide phosphate was detectable in the plasma by 15-60 min after the end of the infusion. The mean half-life of etoposide at the different dose levels ranged from 5.5 to 9.3 h. The pharmacokinetics of etoposide, generated from etoposide phosphate, was linear over the dose range studied and was comparable to results reported in the literature for i.v. etoposide. In summary, i.v. etoposide phosphate is rapidly and extensively converted to etoposide. The maximum tolerated dose of etoposide phosphate when given on days 1, 3, and 5 is 150 mg/m2/day. The dose-limiting toxicity is myelosuppression. The maximum tolerated dose and adverse event profile are consistent with those of etoposide.

Adult↗
PubMed1995

Dose escalation of N,N',N"-triethylenethiophosphoramide combined with pentoxifylline for advanced breast cancer.

Pentoxifylline potentiates the cytotoxicity of alkylating agents in preclinical models. In this study we sought to define the maximum tolerated dose (MTD) of N,N',N"-triethylenethiophosphoramide (thioTEPA) with pentoxifylline, and to estimate the antitumor response to this combination in previously treated breast cancer patients. Thirty-five previously treated advanced breast cancer patients received 70 cycles (median, 2 cycles/patient; range, 1-6) of 1600 mg of oral sustained release pentoxifylline every 8 h for 4 doses in combination with escalating doses of i.v. bolus thioTEPA 40-65 mg/m2 administered 3 h after the second dose of pentoxifylline. Thrombocytopenia was dose limiting at 65 mg/m2 of thioTEPA, and the MTD was defined as 60 mg/m2. Among 25 patients treated at the MTD, leukopenia was grade 2 in 9 patients (36%), grade 3 in 4 patients (16%), and grade 4 in 2 patients (8%); thrombocytopenia was grade 2 in 3 patients (12%), grade 3 in 4 patients (16%), and grade 4 in 3 patients (12%). No other thioTEPA-related toxicity was observed. Plasma concentrations of thioTEPA, TEPA, and pentoxifylline were measured in 6 patients. The median (range) area under the plasma concentration versus time curve for thioTEPA was 29.4 microM/h (26. 2-40.5) and for TEPA was 16.3 microM/h (9.2-21.7 microM-h). The median (range) maximal plasma concentration of pentoxifylline and major metabolites I, IV, and V were 1.2 microgram/ml (0.2-7.8), 4.0 microgram/ml (0.5-16.4), 0.4 (range 0.1-0.8), and 2.9 (1.1-5.5), respectively. No objective responses were observed among 21 evaluable patients treated at the MTD (95% confidence interval, 0-15%). The combination of pentoxifylline and thioTEPA is well tolerated but not active in previously treated advanced breast cancer patients. Further clinical trials using commercially available oral sustained release pentoxifylline as a modulator of alkylating agents are not warranted.

Administration, Oral↗
PubMed1994

CD3+, CD56+ aggressive variant of large granular lymphocyte leukemia.

Clonal expansions of CD3+ large granular lymphocytes (LGL) have been classified as T-LGL leukemia. The majority of patients with T-LGL leukemia have a chronic disease (years) manifested often by severe neutropenia, rheumatoid arthritis, and mild-to-moderate splenomegaly. The characteristic phenotype of the leukemic LGL is CD3+, CD8+, CD16+, CD57+, and CD56-. In this report we describe an aggressive variant of T-LGL leukemia in which leukemic LGL also expressed CD56, as identified by two-color flow-cytometry analysis. In contrast to the chronic nature typical of T-LGL leukemia, these patients presented with a severe systemic illness that was rapidly progressive and resistant to treatment. Atypical clinical features included rapidly increasing spleen size to massive proportions, extensive lymphadenopathy, and the presence of B symptoms (fever, nightsweats, weight loss). Hematologic and pathologic features were also unusual for T-LGL leukemia. These patients had very high LGL counts at diagnosis (range 11,692 to 26,312 microL), which increased rapidly despite treatment. Histopathologic examination of splenic sections showed extensive infiltration of red pulp cords and sinuses by leukemic cells with atrophy of the white pulp. These clinicopathologic features are similar to those described for patients with natural killer cell (NK)-LGL leukemia, whose cells are also CD56+. However, unlike NK-LGL leukemia, we could not show a direct pathogenic role for Epstein-Barr virus (EBV), as Southern-blot analyses using an EBV-joined termini probe were negative in these patients. Our findings suggest that CD3+, CD56+ LGL leukemia is a distinct clinicopathologic entity separate from the usual CD3+, CD56- T-LGL leukemia. The expression on leukemic LGL of CD56, an adhesion molecule, may determine the aggressive biologic nature of this newly described disease.

Adolescent↗