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Biomedical subjects

L Elliott

Publications and source records attributed to L Elliott.

At least 55 records · Page 3Linked to original sources

Inhibition of anti-CD3 monoclonal antibody-induced T-cell proliferation and interleukin-2 secretion by physiologic combinations of dexamethasone and prostaglandin E2.

1. The purpose of these studies was to characterize further previous observations from our laboratory indicating that physiologic concentrations of dexamethasone (DEX) and prostaglandin E2 (PGE2) added together result in synergistic inhibition of the proliferative response of T cells stimulated via the T-cell receptor CD3 signaling complex (TCR/CD3). 2. Various physiologic concentrations of DEX and PGE2 were added to T cells stimulated with immobilized anti-CD3 monoclonal antibody (mAb) and cultured at optimal and suboptimal cell densities. The results demonstrate that the proliferative response of anti-CD3 mAb-stimulated T cells cultured at a suboptimal cell density is more suppressed than that of T cells cultured at optimal concentrations. 3. The proliferative response of CD4+ T cells to immobilized anti-CD3 mAb was also determined in the presence of PGE2 and DEX. The data indicate that the CD4+ subset of T cells is more sensitive to the synergistic antiproliferative effects of DEX and PGE2 compared to whole T-cell populations. 4. Various concentrations of DEX and/or PGE2 were added to T cells stimulated with anti-CD3 mAb and the secretion of interleukin-2 (IL-2) was determined. The results demonstrate that concentrations of DEX and PGE2 which individually do not significantly suppress IL-2 synthesis act together to inhibit the synthesis of IL-2 synergistically. 5. The addition of an exogenous source of recombinant IL-2 (rIL-2) to T cells stimulated in the presence of DEX and PGE2 completely reversed the synergistic antiproliferative effect of these two compounds. This reversal was even more pronounced with T cells cultured at a suboptimal cell density. Additionally, PGE2 and DEX did not affect expression of the IL-2 receptor (IL-2R), as measured by upregulation of the alpha chain, on anti-CD3 mAb stimulated T cells. 6. Collectively these data indicate that physiologic concentrations of PGE2 and DEX, which alone have no effect on anti-CD3 mAb-induced T-cell proliferation, act synergistically to inhibit T-cell proliferation as well as IL-2 synthesis.

Antibodies, Monoclonal↗

The use of external, noninvasive pacing for the termination of supraventricular tachycardia in the emergency department setting.

STUDY OBJECTIVE: To determine the potential feasibility of external cardiac pacing for the termination of sustained supraventricular tachycardia in the emergency department setting. TYPE OF PARTICIPANTS: Three men and two women (mean age, 34 years) who presented to the ED with a narrow-complex, hemodynamically stable tachycardia that was later proven to be supraventricular in origin. INTERVENTION: Each patient underwent external overdrive pacing using a modified external pacemaker at a pulse amplitude of 120 mA and a rate between 240 and 280 pulses per minute. RESULTS: In four patients, external cardiac pacing was able to successfully terminate the tachycardia without complication. In one patient, the pacemaker was not able to terminate the tachycardia. CONCLUSION: We conclude that external, noninvasive pacing is a feasible means of terminating supraventricular tachycardia in the ED setting.

Adult↗

Discriminating needle exchange attenders from non-attenders.

In 1990, approximately 1500 of Glasgow's estimated 9400 injecting drug users attended the city's four needle and syringe exchanges. In the same year, a multisite and citywide strategy was used to interview an estimated 5% sample of the city's injectors using an internationally agreed WHO structured schedule. Of the 503 injectors who participated in the study 54% (n = 272) had made use of exchanges in the last 6 months (including 165 injectors recruited from exchanges), while the remaining 46% (n = 231) had not. Twenty-seven variables were entered into a stepwise discriminant analysis to predict group membership (attenders vs. non-attenders). Fourteen variables emerged in the final discriminant function, which explained 17.3% of the variance between the two groups. Comparison of the model to random classification of cases resulted in a third fewer cases being wrongly assigned. Needle exchange attenders report injecting fewer drugs, less injecting with and passing on of used equipment and greater use of condoms with casual partners, compared to non-attenders. They also had greater knowledge of AIDS and had made and maintained more harm reduction changes, although they were less likely to have received treatment than non-attenders. The finding that attenders were less likely to inject with or pass on used needles and syringes is discussed in the context of availability of clean equipment and perception of risk. Variables reflecting lifestyle such as housing, employment and prison experience were not found to have any discriminatory power.

Acquired Immunodeficiency Syndrome↗

Usefulness of fluoxetine hydrochloride for prevention of resistant upright tilt induced syncope.

Recurrent vasovagally mediated episodes of hypotension and bradycardia are a common cause of recurrent syncope that can be identified by head-upright tilt table testing. Although the use of beta blockers, transdermal scopolamine, disopyramide, and fludrocortisone may be helpful in preventing further episodes, some patients are intolerant of or respond poorly to each of these agents. Following anecdotal observations, we investigated the utility of fluoxetine (a serotonin re-uptake antagonist) in preventing head-upright tilt induced hypotension/bradycardia in patients unresponsive to or intolerant of standard therapy. Sixteen patients (7 men and 9 women, mean age 42 +/- 21 years) with recurrent syncope and positive head-upright tilt studies (refractory to normal therapy) were placed on fluoxetine and restudied 5-6 weeks afterward. Three patients were intolerant of the medication. Of the 13 patients who underwent repeat tilt studies, seven patients (53% of the patients retested or 44% of the total group) were rendered tilt table negative, and, over a mean follow-up period of 19 +/- 9 months, have remained asymptomatic. We conclude that fluoxetine may be an effective therapy in patients with recurrent vasovagally mediated syncope refractory to other forms of therapy.

Adult↗

Adaptive rate pacing controlled by right ventricular preejection interval for severe refractory orthostatic hypotension.

A 72-year-old African-American man with frequent recurrent syncope was found to have severe refractory orthostatic hypotension with concomitant supine hypertension. Pharmacotherapy was successful in controlling his supine hypertension but was unable to resolve his severe orthostatic hypotension. Temporary fixed rate tachypacing was only minimally effective in preventing syncope during upright tilt, while variable rate pacing based on degree of blood pressure fall was far superior. Following these observations, an adaptive rate pacing system controlled by right ventricular preejection interval was implanted (Precept DR Model 1200). The system adequately sensed the patient's fall in blood pressure when sitting or standing and augmented its rate accordingly, thus preventing syncope. While supine, the pacing rate fell to 60 ppm, thereby, avoiding an exacerbation of his concomitant supine hypertension. Over a 3-month follow-up period, he has had no further orthostatic or syncopal episodes. We conclude that adaptive rate pacing using right ventricular preejection interval may be an effective treatment for severe refractory orthostatic hypotension.

Aged↗

Tilt table testing in the evaluation and management of athletes with recurrent exercise-induced syncope.

Recurrent idiopathic exercise-related syncope in the young athlete is often a challenging and frustrating condition. Vasovagally mediated hypotension and bradycardia is believed to be a common, but difficult to prove, cause of this form of syncope. This study evaluated the usefulness of head-upright tilt table testing in the evaluation and management of young athletes with recurrent idiopathic exercise-related syncope. Twenty-four trained young athletes (12 male, 12 female mean age 18 +/- 3.4 yr) with recurrent unexplained exercise-related syncope were evaluated by use of an upright tilt table test for 30 min, with or without an infusion of isoproterenol (1-3 micrograms.min-1 given intravenously) in an effort to provoke bradycardia, hypotension, or both. Ten control patients with no history of syncope were also studied. Syncope occurred in 10 patients (41%) during the baseline tilt and in nine patients (37%) during the isoproterenol infusion (total positives 79%). Seventeen patients who had positive test results eventually became tilt table negative with pharmacotherapy, and over a mean follow-up period of 23 +/- 7 months, no further syncopal episodes have occurred. Two patients refused pharmacotherapy and have continued to experience syncope. We conclude that head-upright tilt table testing combined with isoproterenol infusion is useful in the diagnosis of vasovagal syncope in young athletes with recurrent exercise related syncope, and in the evaluation of prophylactic pharmacotherapy.

Adolescent↗

Laparoscopic cholecystectomy: comparison of university and community experience.

We compared the first year's experience in performing laparoscopic cholecystectomy in a university hospital and a community hospital to determine the impact of postgraduate surgical training on outcome. Laparoscopic cholecystectomy was attempted on 446 patients. The conversion rate to open cholecystectomy was 8.3% and did not differ between institutions. Surgical house staff performed 43% of the cases at the university hospital compared with 8% at the community hospital. The greater use of laser and cholangiograms resulted in significantly longer mean operative time at the university hospital (141 +/- 26 min) than at the community hospital (114 +/- 52 min). The overall complication rate did not differ significantly (p = 0.15). Complications included common duct injury (three cases), bile leak (five cases), bleeding or hematoma (six cases), epigastric artery hematoma (one case), and death (one case). Operative inexperience during this first year may be a major determinant for the complication rates at both hospitals. It is too early to determine the impact of graduate surgical education on complications. Intense education and supervised instruction is requisite to minimizing the morbidity associated with laparoscopic cholecystectomy regardless of whether it is performed at a university or community hospital.

Adolescent↗

Inhibition of anti-CD3 monoclonal antibody-induced T-cell proliferation by dexamethasone, isoproterenol, or prostaglandin E2 either alone or in combination.

1. The purpose of these studies was to investigate the modulation of the proliferation of human T cells obtained from peripheral blood by dexamethasone (DEX), isoproterenol (ISO), and prostaglandin E2 (PGE2). The former two substances interact with T cells via the glucocorticoid and beta-adrenergic receptors respectively. When occupied by their natural ligands, glucocorticosteroids and catecholamines, these receptors have a role in modulating T-cell function during stress. During the inflammatory response increased levels of PGE2 bind to their receptors on T cells and thus alter responsiveness. Proliferation of T cells was induced by immobilized anti-CD3 monoclonal antibody (mAb) in the presence or absence of an additional costimulatory signal delivered by anti-CD28 mAb. 2. Various physiologic concentrations of DEX, ISO, or PGE2 were added at the time of initiation of the cultures and subsequent proliferation of the unstimulated T cells was determined. The results demonstrate that physiologic concentrations of all three of these agents inhibit the anti-CD3 mAb-induced proliferation of T cells. 3. Although DEX and PGE2 were equipotent in suppressing T-cell proliferation, ISO was much less effective. 4. Because concomitant elevations in the peripheral levels of these substances may occur, experiments were performed to determine the T-cell inhibitory effects of DEX together with either PGE2 or ISO. Synergistic suppression of T-cell proliferation was observed when various concentrations of DEX and PGE2, but not DEX and ISO, were added to cultures. This synergistic suppression could not be explained by an increase in cAMP accumulation in T cells stimulated with DEX and PGE2. 5. Finally, the addition of anti-CD28 mAb to anti-CD3 mAb-stimulated T cells overcame much of the suppression of proliferation induced by PGE2 or ISO but less so than that induced by DEX.

Antibodies, Monoclonal↗

Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.

The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic.

Administration, Oral↗

The use of external, noninvasive pacing for the termination of ventricular tachycardia in the emergency department setting.

STUDY OBJECTIVE: To determine the potential usefulness of external cardiac pacing for the termination of sustained ventricular tachycardia in the emergency department setting. TYPE OF PARTICIPANTS: Five men and one woman (mean age, 57 years) who presented to the ED with a wide-complex, hemodynamically stable tachycardia that was later proven to be ventricular in origin. INTERVENTION: Each patient underwent external overdrive pacing using a modified external pacemaker at a pulse amplitude of 120 mA and a rate of 200 pulses per minute. RESULTS: In all six patients, external cardiac pacing was able to successfully terminate tachycardia without complication. CONCLUSION: We conclude that external noninvasive pacing may be an effective means of terminating ventricular tachycardia in the ED setting.

Adult↗

Differences in HIV-related knowledge and attitudes between Caucasian and 'Asian' men in Glasgow.

There is little available information about the possible differences in HIV-related knowledge and attitudes between ethnic majority and minority groups. Questionnaires were completed by 490 Caucasian males and 243 males with origins in the Indian subcontinent ('Asian') living in Glasgow. There were small differences between the samples regarding knowledge of modes of transmission of HIV or perceived adequacy of personal knowledge. The 'Asian' men, however, were much more likely to indicate reluctance to use services also used by people with HIV and to feel that people with AIDS only had themselves to blame. They were also much less likely to feel at risk of becoming infected with HIV. The differences were not related to age. These marked differences, apparently unrelated to knowledge are important and require further exploration.

Adult↗

Recurrent unexplained syncope in the elderly: the use of head-upright tilt table testing in evaluation and management.

OBJECTIVE: To investigate the usefulness of head-upright tilt table testing for vasovagal episodes in the evaluation and management of elderly patients with recurrent idiopathic syncope. DESIGN: Prospective survey. SETTING: Electrophysiology laboratory of a university hospital. PATIENTS: Twenty-five patients (11 male, 14 female; mean age 73 +/- 6 years) with recurrent unexplained syncope and seven control subjects with other causes of syncope (4 male, 3 female; mean age 70 +/- 4 years). METHODS: Each patient underwent head-upright tilt table testing for 30 minutes with or without an infusion of isoproterenol (1-3 micrograms/min given intravenously) in an attempt to provoke bradycardia, hypotension, or both. MAIN RESULTS: Syncope occurred in nine patients (36%) during the baseline tilt and in seven patients (28%) during isoproterenol infusion (total positives 64%). None of the controls had syncope during the test. All of the patients who had positive test results eventually became tilt table negative with therapy, and over a mean follow-up period of 24 months, no further syncopal episodes have occurred. CONCLUSIONS: Head-upright tilt table testing combined with isoproterenol infusion may be a useful tool in the diagnosis of vasovagal syncope in the elderly and in the evaluation of preventive therapy.

Aged↗

Reproducibility of head upright tilt table test results in patients with syncope.

Head upright tilt table testing is a promising technique for the evaluation and management of vasovagal (neuroregulatory) syncope. In order to determine the day-to-day reproducibility of results using this technique we performed head upright tilt table testing (with or without graded isoproterenol infusion) in 21 patients (12 males, 9 females, mean age 34 +/- 19.1 years). During the first tilt study a total of 14 patients experienced syncope (six during baseline tilt, mean tilt time 15.8 +/- 7 minutes, eight following tilt with graded isoproterenol infusion, mean tilt time 17.7 +/- 9 minutes) while seven were negative. During the second tilt study (performed 3-7 days following the first study) the results of the first study were duplicated in 19 patients (90%) (six during baseline tilt, mean time 17.5 +/- 8 minutes, eight following graded isoproterenol infusion, mean time 15.9 +/- 7 minutes), however the level of provocation required to provoke syncope differed from that needed in the initial test in five patients (24%). We conclude that the results of head upright tilt table testing with graded isoproterenol infusions can be duplicated in 90% of patients, although some day-to-day variability exists in the degree of provocation necessary to elicit a positive response.

Adult↗

Tachycardia sensing failure of an implantable cardioverter defibrillator in a patient with hypertrophic cardiomyopathy.

A 17-year-old white male was found to have nonobstructive hypertrophic cardiomyopathy after suffering three severe syncopal episodes. He experienced an episode of sustained polymorphic ventricular tachycardia during exercise tolerance testing that required cardioversion. Electrophysiological studies were able to reproduce sustained polymorphic ventricular tachycardia that was unresponsive to standard pharmacotherapy. An automatic implantable defibrillator was placed. However, during implantation with the rate sensing electrodes on the left ventricle, it was found that the extremely polymorphic nature of the tachycardia caused such rapid fluctuations in the sensed R wave signal that the device could not properly detect the tachycardia. This was felt to be due to the automatic gain control circuit of the Ventak 1550. The problem was solved by moving the rate sensing electrodes to the lateral right ventricle. This case suggests that the unique arrhythmic substrate of hypertrophic cardiomyopathy may present sensing difficulties during automatic implantable defibrillator insertion.

Adolescent↗