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Biomedical subjects

D Stewart

Publications and source records attributed to D Stewart.

At least 271 records · Page 15Linked to original sources
PubMed1989

Inhibition of murine lymphokine-activated killer (LAK) cell activity by adherent cells.

The effects of adherent cell depletion, indomethacin, and prostaglandin E2 (PGE2) on murine LAK cell activity were investigated. Removal of plastic adherent cells from splenocyte suspensions either prior to 5-day culture with 1000 U/ml of recombinant human IL-2 (rIL-2) or prior to assay resulted in an enhanced LAK cell cytotoxicity compared to that of whole spleen cell suspensions. Indomethacin enhanced LAK cell cytotoxicity of whole splenocyte suspensions if present during the culture period, but had no effect on whole splenocyte or adherent cell-depleted cell suspensions if added just prior to assay. PGE2 suppressed LAK cell activity of nonadherent splenocyte but not whole splenocyte suspensions when present during the culture period. In vivo treatment of mice with indomethacin enhanced cytotoxicity directed toward both LAK sensitive, natural killer (NK) resistant (P-815) and LAK, NK sensitive (YAC-1) tumor cell targets. Splenocytes from indomethacin-treated mice cultured with additional indomethacin and rIL-2 exhibited highest LAK cell activity. The results from this study indicate that LAK cells are regulated by adherent cells which suppress LAK cell activity. This suppression can be reversed both in vitro and in vivo by indomethacin. This study has important implications for the possible clinical use of indomethacin in the potentiation of in vivo and in vitro LAK cell activity for immunotherapeutic protocols.

Animals↗
PubMed1989

The prognostic significance of quantitative signal-averaged variables relative to clinical variables, site of myocardial infarction, ejection fraction and ventricular premature beats: a prospective study.

A prospective study was undertaken of the prognostic significance of quantitative signal-averaged electrocardiographic (ECG) variables relative to clinical variables, site of myocardial infarction, left ventricular ejection fraction and characteristics of ventricular premature beats in 115 patients (mean age 62 +/- 12 years) studied 10 +/- 6 days after myocardial infarction. Signal-averaged variables included the root mean square voltage of the terminal 40 ms, the duration of the filtered signal-averaged QRS complex and low amplitude signals less than 40 microV determined at 25 and 40 Hz high pass filtering in all patients. Of the 115 patients, 51 (44%) had an abnormal signal-averaged ECG (one or more abnormal signal-averaged variables), 51 (44%) at 25 Hz and 48 (42%) at 40 Hz high pass filtering. A higher proportion of patients with an inferior wall infarction had an abnormal signal-averaged ECG as compared with patients with anterior wall infarction (58% versus 31%). Over a 14 +/- 8 month follow-up period 16 patients (14%) had an arrhythmic event. An abnormal signal-averaged ECG at 40 Hz high pass filtering had a higher sensitivity (81% versus 75%) and specificity (65% versus 61%) than at 25 Hz high pass filtering. The predictive value of the signal-averaged ECG was superior to that of the ejection fraction (40% versus 20%) in anterior wall myocardial infarction, whereas in patients with inferior wall infarction, the predictive values of the two tests were equivalent. The prognostic power of 27 clinical and noninvasive variables was determined with the Cox proportional hazards regression model.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Detection of brain death in barbiturate coma: the dilemma of an intracranial pulse.

Patients treated with barbiturate coma for elevated intracranial pressure after head injury may suffer brain death. Since such patients have an iatrogenically induced absence of neurological function, brain death cannot be diagnosed clinically. Furthermore, as demonstrated by two of our patients, monitoring of intracranial pressure, even in the face of brain death, may show a low intracranial pressure and an intracranial pulse, suggesting the presence of adequate cerebral perfusion pressure and, therefore, brain viability. Under these circumstances, however, significant intracranial blood flow may be absent. Therefore, we suggest that a patient in barbiturate coma should undergo serial blood flow studies, even when the intracranial pressure is low and an intracranial pulse is present, to determine whether brain death has occurred.

Adult↗
PubMed1989

Intraarterial cisplatin and concurrent radiation for locally advanced bladder cancer.

Between 1983 and 1987 25 patients with invasive bladder cancer (16 stage tumor 3 (T3) and nine stage T4) were treated with intraarterial cisplatin and concurrent radical radiation (20/25) or intraarterial cisplatin, concurrent preoperative radiation, and cystectomy (5/25). One patient died from treatment-related toxicity. Other toxicities have been what one would expect from the individual treatment modalities except for a sensory sacral root neuropathy in 11 of 24 (46%) patients. Twenty-three of 24 (96%) patients achieved a complete response (CR) and the projected actuarial 2-year survival is 90%. Only one of the 23 complete responders has had an invasive local recurrence. The excellent complete local response and survival rates achieved warrant further study of the combination of intraarterial cisplatin and radiation as a bladder-preserving strategy.

Aged↗
PubMed1989

Occupational hot exposures: a review of heat and mass transfer theory.

The assessment and control of hot working environments is based on an appraisal of the thermal interaction between an individual and the surroundings. This paper examines in detail the processes of convection, radiation and evaporation which constitute the principal mechanisms for this interaction. The defining equations are discussed with particular attention given to the appropriate numerical values of body heat and mass transfer coefficients. The use of the heat-mass transfer analogy for the prediction of the mass transfer coefficient is introduced and verified. Finally, recommendations are given as to the most appropriate set of energy exchange equations for use in the analysis of high-temperature environments. The physiological criteria involved in hot working conditions, and the generation of a suitable assessment procedure based on the energy exchange equations, are the subject of a companion paper.

Body Surface Area↗
PubMed1989

Occupational hot exposures: body physiology and an approach to numerical assessment.

This paper summarizes the factors which influence the energy exchange processes between an individual and his surroundings and the mechanisms by which the body attempts to maintain itself in a heat balance situation. Thereafter, the important physiological reactions to hot working conditions are described and, on this basis, a numerical assessment procedure is proposed. Examples are given of the use of this method in investigating the possibility of heat stress and estimating the time for which an acclimatized worker can safely be exposed in such circumstances. An increase in the permissible exposure time through a manipulation of the environmental parameters is also considered.

Body Temperature Regulation↗
PubMed1989

Utilization of cholesterol-rich lipoproteins by perfused rat adrenals.

This study describes high density lipoprotein (HDL) uptake in the rat adrenal using a newly developed nonrecycling perfusion technique to control both the quality and quantity of the supplied lipoprotein. The aim of the study was to quantify a nonendocytic (alternative) pathway in the delivery of HDL-cholesterol. All experiments were conducted using an acute lipoprotein-deficient rat model (24 h 4-aminopyrazolo-[3, 4-d]-pyrimidine, 4-APP) in which circulating levels of cholesterol were reduced by one half, but various adrenal gland measurements of cholesterol metabolism were unchanged. Both rat HDL (rHDL) and affinity-purified human HDL3 (hHDL3) were used throughout the study. Microscopic autoradiographs (ARGs) indicate that both ligands bind avidly and exclusively to cells of the adrenal fasciculata and reticularis zones. Despite differences in binding affinity, both ligands deliver approximately the same total cholesterol to the cell interior as estimated by double-labeled residualizing tags on HDL (i.e., 125I-labeled dilactitol tyramine-[3H]cholesteryl linoleyl ether (DTT-CLE) HDL). The internalized cholesterol can account for much of the corticosterone produced during the 90-min time frame; however, only a small fraction of this cholesterol could have been provided via the endocytic pathway. Data obtained with the use of 125I-labeled DTT-[3H]CLE-HDL show that only 8.0% (or 0.7%) of corticosterone produced with rHDL (or hHDL3) could have come from cholesterol internalized as a component of intact HDL (i.e., via the endocytic pathway). These calculations strengthen the electron microscopy autoradiographic data that show that few exposed silver grains (representing the localization of the 125I-isotope) are found within the cell cytoplasm. Thus, despite differences in the uptake characteristics of the two ligands, most of the HDL-cholesterol internalized and used for corticosterone production during adrenal perfusion apparently comes from a pathway in which intact HDL are not internalized.

Adenine↗
PubMed1989

Nail changes associated with systemic disease and vascular insufficiency.

In some cases, nail changes may not only be the presenting sign of systemic disease, but a sensitive indicator of treatment efficacy as well. Awareness of nail dystrophies and their association with underlying pathology can aid the practitioner in the diagnosis and management of the podiatric patient.

Arterial Occlusive Diseases↗
PubMed1989

Undiversion in patients with meningomyelocele.

Since 1981, 12 patients with neurogenic bladder due to meningomyelocele who had had previous ileal conduit urinary diversions underwent assessment for undiversion. Two important criteria for undiversion were motivation and a reconstructable bladder. Four patients either did not fulfil these criteria or refused surgery. Eight patients (six females and two males) underwent undiversions. Uretero-ureteral anastomosis was achieved in 13 ureters and ureteroneocystostomy in 2; transureteroureterostomy was necessary in 1 ureter. Augmentation cystoplasty and vesicourethropexy were important in establishing continence postoperatively; these procedures were not performed in two patients whose undiversion failed early in the series. The evolution of an investigation protocol, surgical technique and final approach to this complex problem are discussed.

Anastomosis, Surgical↗
PubMed1989

An outbreak of salmonellosis amongst holidaymakers in Madeira, July 1988.

In July 1988, 20 of 49 tourists from Northern Ireland became ill with gastrointestinal symptoms while on holiday in Madeira and four were admitted to hospital. Salmonella enteritidis was subsequently isolated from eight members of the party. Epidemiological investigations implicated fried and/or scrambled eggs as the vehicle of infection.

Disease Outbreaks↗
PubMed1989

Perinatal mortality in Northern Ireland: where are we now?

Perinatal mortality in Northern Ireland has been declining over the last 30 years, but the factors which may account for this fall have not been clearly delineated. Crude perinatal mortality figures yield very little insight into the problem, and meaningful management statistics are urgently required if service performance is to be reasonably assessed. This paper sets out the case for birth-weight standardisation and explores the utility of a broad diagnostic taxonomy of causes of death.

Birth Weight↗
PubMed1988

Brain metastases with an unknown primary: a clinical perspective.

A review of 43 patients with cerebral metastases, an unknown primary, and no other sites of metastases is presented. 27/43 (62.7%) had solitary metastases and 37.2% (16/43) had multiple metastases. Surgical treatment involved complete resection in 30.2%, subtotal resection in 37.2% and biopsy alone or no surgical procedure in the remainder. 39/43 patients underwent whole brain irradiation with the majority receiving 3,000-4,000 rads/10-20 fractions. Overall survival was 52% at six months and 20% at one year, and was significantly better in patients with solitary as opposed to multiple metastases (p less than 0.03). A failure analysis including autopsy data demonstrates that (28/41) 68.3% of patients died of progressive intracranial disease without extracerebral metastases. Implications for treatment strategies are discussed.

Actuarial Analysis↗
PubMed1988

Role of signal averaging of the surface QRS complex in selecting patients with nonsustained ventricular tachycardia and high grade ventricular arrhythmias for programmed ventricular stimulation.

Signal averaging of the surface QRS complex was performed before programmed ventricular stimulation in 53 individuals with high grade ventricular arrhythmias or nonsustained ventricular tachycardia, or both. An abnormal signal-averaged electrocardiogram (ECG) was recorded in 22 patients and was associated with inducible ventricular tachycardia in 12 (55%) of the 22. In contrast, a normal signal-average ECG was associated with inducible tachycardia in only 1 (3%) of 31 individuals (p less than 0.005). The group with inducible tachycardia had a longer duration of the signal-averaged QRS complex (124 +/- 19 versus 96 +/- 26 ms) and of low amplitude signals (44 +/- 13 versus 29 +/- 11 ms) (p less than 0.005). In addition, the root mean square voltage of the terminal 40 ms was lower in this group (20 +/- 14 versus 48 +/- 34 microV, p less than 0.005). Twenty-seven of the 53 subjects had a prior myocardial infarction; 17 (63%) of the 27 had an abnormal signal-averaged ECG, and ventricular tachycardia was inducible in 10 (59%) of the 17. A normal signal-averaged ECG was recorded in 10 of the 27 patients and only 1 (10%) of these 10 had inducible tachycardia. An abnormal signal-averaged ECG had a 91% sensitivity and a 56% specificity with respect to subsequent induction of tachycardia. During long-term follow-up, 2 (15%) of the 13 patients with inducible ventricular tachycardia who were treated with electrophysiologically guided antiarrhythmics therapy died suddenly; the remaining 11 patients (85%) are alive 15 +/- 10 months after electrophysiologic testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Strain Improvement of Rhodotorula graminis for Production of a Novel l-Phenylalanine Ammonia-Lyase.

l-Phenylalanine ammonia-lyase (PAL; EC 4.3.1.5) from Rhodotorula rubra has been used in the commercial manufacture of l-phenylalanine from trans-cinnamic acid. In this study, R. graminis PAL was investigated. Mutant strain GX6000 was isolated after ethyl methanesulfonate mutagenesis of wild-type R. graminis GX5007 by selecting for resistance to phenylpropiolic acid, an analog of trans-cinnamic acid. Mutant strain GX6000 produced inducible PAL at levels four- to fivefold higher than had wild-type R. graminis. Furthermore, this strain had several other physiological traits that make it more commercially useful than R. rubra. For example, during fermentation, the PAL half-life was three- to fivefold longer, PAL specific activity was six to seven times higher, and PAL synthesis was significantly less inhibited by temperatures above 30 degrees C. Induction of PAL in strain GX6000 appeared to be less tightly regulated; l-leucine acted synergistically with l-phenylalanine, the physiological inducer, to increase the PAL specific activity and titer to 165 U/g (dry weight) and 3,000 U/liter, respectively, a 40% increase over the effect of l-phenylalanine alone. Strain GX6000 PAL showed significantly greater stability in bioreactors for the synthesis of l-phenylalanine, a finding that is consistent with the stability properties observed during fermentation.

Journal Article↗
PubMed1988

Bladder-outlet reconstruction in neurogenic bladder due to myelomeningocele.

In a subgroup of children with myelomeningocele, urinary incontinence cannot be managed by clean intermittent catheterization and anticholinergic medication. The authors report on 24 such children who required bladder-outlet reconstruction. Twelve boys underwent the Young-Dees/Leadbetter procedure, 8 girls underwent the Burch procedure and the remaining 4 had a combination of the two. Augmentation cystoplasty was also carried out in seven girls and one boy. Results were most favourable in the girls, with improvement in 92%, in contrast to the boys in whom only 58% were improved. Artificial sphincter placement may be a more beneficial alternative for boys.

Adolescent↗
PubMed1987

Optimal bandpass filters for time-domain analysis of the signal-averaged electrocardiogram.

The optimal bandpass filter for signal averaging of the surface QRS complex to detect late potentials is undefined. A study was conducted in 87 patients; 25 (mean age 34 +/- 10 years) were normal (group I), 29 (60 +/- 20 years) had organic heart disease without ventricular tachycardia (group II) and 33 (62 +/- 15 years) had sustained ventricular tachycardia (group III). In all patients signal-averaged electrocardiography (200 beats) was performed using a sharp, bidirectional filter and data analyzed using the following 7 high-pass filter settings: 10, 15, 20, 25, 40, 80 and 100 Hz. For each filter the duration of the signal-averaged QRS complex, the low-amplitude signals of less than 40 microV and the root-mean-square voltage of the terminal 40 ms (RMS-40) were determined. Normal values for each filter were determined from group I patients. In all 3 groups, quantitative signal-averaged variables were filter dependent. There was a progressive and marked decrease in RMS-40 and a progressive and marked increase in low-amplitude signal duration as the high-pass filtering was increased from 10 to 100 Hz. In contrast, high-pass, filter-dependent changes in signal-averaged QRS duration were less marked. The sensitivity and specificity for each filter using RMS-40 as the index of late potentials in separating group III patients from group II patients were: 10 Hz-64% and 52%; 15 Hz-57% and 72%; 20 Hz-57% and 76%; 25 Hz-42% and 90%; 40 Hz-61% and 83%; 80 Hz-88% and 69%; and 100 Hz-79% and 62%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Affinity labeling of delta-opiate receptors using [D-Ala2,Leu5,Cys6]enkephalin. Covalent attachment via thiol-disulfide exchange.

[D-Ala2,Leu5,Cys6]Enkephalin (DALCE) is a synthetic enkephalin analog which contains a sulfhydryl group. DALCE binds with high affinity to delta-receptors, with moderate affinity to mu-receptors, and with negligible affinity to kappa-receptors. Pretreatment of rat brain membranes with DALCE resulted in concentration-dependent loss of delta-binding sites. Using 2 nM [3H][D-Pen2,D-Pen5]enkephalin (where Pen represents penicillamine) to label delta-sites, 50% loss of sites occurred at about 3 microM DALCE. Loss of sites was not reversed by subsequent incubation in buffer containing 250 mM NaCl and 100 microM guanyl-5'-yl imidodiphosphate (Gpp(NH)p), conditions which cause dissociation of opiate agonists. By contrast, the enkephalin analogs [D-Ala2,D-Leu5]enkephalin, [D-Ser2,Leu5,Thr6]enkephalin, [D-Pen2,D-Pen5]enkephalin, and [D-Ala2,D-Leu5,Lys6]enkephalin were readily dissociated by NaCl and Gpp(NH)p, producing negligible loss at 3 microM. This suggests that DALCE binds covalently to the receptors. Pretreatment of membranes with the reducing agents dithiothreitol and beta-mercaptoethanol had no effect on opiate binding. Thus, loss of sites required both specific recognition by opiate receptors and a thiol group. The irreversible effect of DALCE was completely selective for delta-receptors. Pretreatment with DALCE had no effect on binding of ligands to mu- or kappa-receptors. The effect of DALCE on delta-binding was: 1) markedly attenuated by inclusion of dithiothreitol in the preincubation buffer, 2) partially reversed by subsequent incubation with dithiothreitol, 3) slightly enhanced when converted to the disulfide-linked dimer, and 4) prevented by blocking the DALCE sulfhydryl group with N-ethylmaleimide or iodoacetamide. These results indicate that DALCE binds covalently to delta-receptors by forming a disulfide bond with a sulfhydryl group in the binding site. The mechanism may involve a thiol-disulfide exchange reaction.

Animals↗