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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 91 records · Page 5Linked to original sources

Dying at home: evaluation of a hospice rapid-response service.

Various studies suggest that there is a preference among patients, professionals and the public for death to occur at home (Dunlop et al, 1989; Townsend et al, 1990; Hinton, 1994). Data indicates that some patients are denied the opportunity to exercise choice in the place of death. In areas where palliative rapid-response teams have been available more people have been able to die at home. This article presents the findings of an evaluation of a hospice rapid-response service in the Highlands of Scotland, which was designed to respond to the needs of people in crisis facing death. The study was designed to produce a rigorous and comprehensive description of a newly-operational service at the pilot stage. It reflects not only the views of the professionals involved but also focuses on the views of informal carers. Seventeen patients were referred to the rapid-response service in its first year of operation between April 1998 and March 1999. The service has shown some success in enabling patients to die at home and satisfaction with the service is high among professionals and lay carers.

Community Health Nursing↗

Effect of subacute ibuprofen dosing on rectal mucosal prostaglandin E2 levels in healthy subjects with a history of resected polyps.

Nonsteroidal antiinflammatory drugs are among the most promising chemopreventive agents for colorectal cancer. Although the mechanism by which nonsteroidal antiinflammatory drugs exert such effects remains to be further characterized, their best known pharmacological effect is inhibition of prostaglandin synthetase, which leads to decreases in tissue prostaglandin levels. We conducted a randomized, double-blind, controlled study to examine the effect of daily ibuprofen treatment on the rectal mucosal prostaglandin E2 (PGE2) levels in healthy subjects with a history of resected polyps. Study participants (n = 27) completed a 2-week run-in period and were then randomized to take a single, daily dose of ibuprofen (300 or 600 mg) or of a placebo for 4 weeks. Rectal biopsy specimens were taken before and after the run-in period and at 2 and 4 weeks after the ibuprofen/placebo treatment. Notably large between- and within-subject variability in the rectal mucosal PGE2 content was seen. The changes in PGE2 levels after ibuprofen/placebo treatment correlated with the baseline PGE2 content. After adjustment of the baseline values, 2 weeks of 300 mg/day of ibuprofen treatment resulted in significantly more suppression of PGE2 levels than that observed after the placebo treatment (55% versus 22% suppression from baseline; P = 0.033). Although other ibuprofen treatment schedules and doses appeared to result in suppression in the PGE2 levels, the suppression was not statistically significant because of the large variability in this measurement. Because lower doses are associated with fewer adverse effects, a dose of 300 mg of ibuprofen/day should be considered for future Phase II chemoprevention studies. Stratifying study participants, based on their baseline PGE2 levels and inclusion of a larger number of study subjects, are recommended for future trials where the rectal mucosal PGE2 level is to be used as a surrogate end point biomarker.

Adult↗

Pharmacological treatments for alcoholism: revisiting lithium and considering buspirone.

OBJECTIVE: Previous research has suggested that both lithium and buspirone could lessen alcoholics' desire to drink as well as reduce the actual amounts of alcohol consumed. The purpose of this study was to compare lithium and buspirone monotherapy with placebo on outcomes of abstinence, alcohol quantity consumed, treatment retention and compliance, and medication side effects. METHODS: We conducted a randomized, double-blind, placebo-controlled, three-arm parallel group, clinical trial that compared lithium and buspirone with placebo in 156 alcohol-dependent men. RESULTS: Study retention rates for the three treatment groups at 3 and 6 months, respectively, were 61% and 46% for lithium, 44% and 27% for buspirone, and 52% and 38% for placebo (p = NS, for 3 and 6 months). Overall abstinence rates were 28% and 19% at 3 and 6 months, respectively. However, mean daily quantities of alcohol consumed and percentage of drinking days decreased significantly (p < 0.0001) over time in all treatment groups. Differential improvement was seen only for the decrement in quantity consumed in the buspirone group, compared with the placebo group, but only at a trend level (p = 0.07). According to pill counts, compliance did not differ significantly among the treatment groups. CONCLUSIONS: These results do not support the hypothesis that either lithium or buspirone, compared with placebo, produces differential reductions in alcohol consumption. The results suggest the need to enhance treatment retention to maximize outcomes.

Adult↗

The management of depression: the implications for managed care--roundtable discussion: Part 2.

One of the most commonly utilized drug classes today is antidepressant therapy, which accounts for billions of dollars in spending. Pharmacoeconomic tools may play an influential role in formulary decision making, particularly in this drug class. In part 2 of the roundtable discussion, a pharmacoeconomic model is presented that may clarify the health economic effects of placing serotonin-norepinephrine reuptake inhibitors on the drug formulary, particularly in the context of other antidepressant medications.

Antidepressive Agents↗

Scintimammography: an adjunctive test for the detection of breast cancer.

OBJECTIVE: To describe the diagnostic utility of scintimammography in patients with a breast mass, including patients who have undergone previous breast surgery or radiotherapy. DESIGN: Descriptive outcome study. SETTING: A university teaching hospital and a private hospital breast clinic in New South Wales. SUBJECTS: 115 consecutively referred women investigated by x-ray mammography and scintimammography before surgical excision biopsy of a breast mass. MAIN OUTCOME MEASURES: Sensitivity and specificity of x-ray mammography and scintimammography in the detection of breast cancer overall, and in women who had or had not undergone previous breast surgery. RESULTS: 44 (38%) patients had undergone previous breast surgery or external beam radiotherapy, including nine with bilateral silicone breast implants. The overall (n = 115) sensitivity for the detection of breast cancer with scintimammography was 84%, compared with 66% for x-ray mammography (P = 0.004), and the respective specificities were 84% and 67% (P = 0.194). For patients who had a history of previous breast surgery, the respective sensitivities of the two tests were 83% and 50% (P = 0.006), compared with 85% and 73% (P = 0.087) for patients who had had no previous surgery. CONCLUSIONS: Scintimammography offers additional diagnostic advantage in the detection of breast cancer in patients who have had previous breast surgery or local radiotherapy.

Adult↗

Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons.

Evidence suggests that a process analogous to long-term potentiation (LTP) may underlie the enhanced behavioural responses attending chronic administration of amphetamine and cocaine in animals (behavioural sensitization). Augmented excitatory amino acid (EAA)-mediated transmission at the level of midbrain dopamine neurons has been implicated as a change critical to the development of sensitization. Here we provide an initial demonstration that EAA synapses on dopamine neurons can undergo plasticity. Tetanic stimulation of the subthalamic nucleus induced a long-lasting increase (39.2 +/- 10.4%) in the amplitude of excitatory postsynaptic potentials recorded in dopamine neurons of the substantia nigra. This LTP, which did not occur in the presence of NMDA antagonists, may constitute the mechanism that lies at the heart of sensitization.

Animals↗

A multi-institutional study of factors associated with fetal death in injured pregnant patients.

HYPOTHESIS: Factors associated with fetal death in injured pregnant patients are related to increasing injury severity and abnormal maternal physiologic profile. DESIGN: A multi-institutional retrospective study of 13 level I and level II trauma centers from 1992 to 1996. MAIN OUTCOME MEASURE: Fetal survival. RESULTS: Of 27,715 female admissions, there were 372 injured pregnant patients (1.3%); 84% had blunt injuries and 16% had penetrating injuries. There were 14 maternal deaths (3.8%) and 35 fetal deaths (9.4%). The population suffering fetal death had higher injury severity scores (P<.001), lower Glascow Coma Scale scores (P<.001), and lower admitting maternal pH (P = .002). Most women who lost their fetus arrived in shock (P = .005) or had a fetal heart rate of less than 110 beats/min at some time during their hospitalization (P<.001). An Injury Severity Score greater than 25 was associated with a 50% incidence of fetal death. Placental abruption was the most frequent complication, occurring in 3.5% of patients and associated with 54% mortality. Cardiotrophic monitoring to detect potentially threatening fetal heart rates was performed on only 61% of pregnant women in their third trimester. Of these patients, 7 had abnormalities on cardiotrophic monitoring and underwent successful cesarean delivery. CONCLUSIONS: Fetal death was more likely with greater severity of injury. Cardiotrophic monitoring is underused in injured pregnant patients in their third trimester even after admission to major trauma centers. Increased use of cardiotrophic monitoring may decrease the mortality caused by placental abruption.

Female↗

Lessons learned from the review of cardiac catheterization laboratories: a report from the Laboratory Survey Committee of the Society for Cardiac Angiography and Interventions.

The Laboratory Survey Committee of the Society for Cardiac Angiography and Interventions was created as a resource for physicians and administrators to provide comprehensive independent outside review services for cardiac catheterization laboratories. Since 1989, when the committee began its work, surveys of 23 catheterization laboratories have been completed. Our review of this experience identified several recurring problems among the laboratories. The purpose of this paper is to summarize our experience and highlight the lessons we learned in the hope that this information will benefit many other laboratories.

Cardiac Catheterization↗

Technetium-99m sestamibi scintimammography: the influence of histopathological characteristics, lesion size and the presence of carcinoma in situ in the detection of breast carcinoma.

The limit of detection of invasive carcinoma by scintimammography appears to be >10 mm, but not uncommonly smaller invasive carcinoma is detected in the presence of pre-invasive carcinoma (carcinoma in situ). The aims of this study were to determine whether a relationship exists between the presence of carcinoma in situ and the detection of invasive carcinoma using scintimammography, and to further characterise the influence of lesion size and histopathological characteristics on the diagnostic accuracy of scintimammography for the detection of invasive breast carcinoma. One hundred and seventeen patients were studied prospectively by scintimammography, X-ray mammography and, where appropriate, breast ultrasound prior to excision biopsy of all suspicious breast masses (n=123, 93% palpable). Thirty-five of these patients had a history of previous ipsilateral breast carcinoma. Sixteen percent of biopsy specimens were benign. The remaining specimens were malignant or pre-malignant. The overall diagnostic sensitivity of scintimammography was 84% and the specificity was 80%. The overall sensitivity and specificity for X-ray mammography (n=123), including those examinations combined with breast ultrasound (n=76), were 73% and 69%, respectively. The maximum size of the measured invasive carcinoma ranged from 5 to 80 mm (median 20 mm). Although the maximum size detected for invasive carcinoma in the presence of carcinoma in situ ranged from 3 to 40 mm (median 20 mm), this difference was not statistically significant (P=1.10, t test). Seven cases of carcinoma in situ were not detected by scintimammography. The diagnostic sensitivity of scintimammography for the detection of invasive carcinoma was 98% for lesions 16-25 mm, 91% for lesions 11-25 mm, 78% for lesions >25 mm and 55% for lesions <11 mm. Scintimammography may offer increased diagnostic accuracy for the detection of breast carcinoma, thereby complementing anatomical imaging. This is particularly evident in technically difficult patients who have had previously treated breast cancer. There appears to be no difference in the diagnostic sensitivity of scintimammography for the detection of invasive carcinoma in the presence or absence of carcinoma in situ.

Biopsy, Needle↗

'Total pain', disciplinary power and the body in the work of Cicely Saunders, 1958-1967.

Pain first emerged as an area of clinical specialisation in the 1950s, but more recently has attracted wider interest from social scientists and clinicians who seek to expand its understanding to incorporate ideas about meaning, embodiment and culture. So far there have been few empirical studies which focus on how ideas and practices about pain are changing in modern healthcare. This paper addresses these issues through a specific case study of the early writings of Cicely Saunders in the period 1958-1967. A professional training in the three disciplines of nursing, social work and medicine, coupled with a strong personal religious faith, provided the biographical context for the development of Cicely Saunders' concern with pain. Through these influences we find in her work with dying patients an emphasis on pain as a key which unlocks other problems and as something which requires multiple interventions for its resolution. From here the concept of 'total pain' is formulated, to include physical, psychological, social, emotional and spiritual elements. This concept, which proved so important to the development of hospice clinical practice, is shown to have paradoxical and conflicting implications. Adopting current ideas about the social theory of the body, 'total pain' may be formulated either as a nomenclature of inscription, or as a nomenclature of facilitation. It is suggested that both of these may be at work in the discourse of 'total pain' and that an appreciation of each enhances our understanding of the concept.

England↗

Stimulation of the pedunculopontine tegmental nucleus in the rat produces burst firing in A9 dopaminergic neurons.

Stimulation of the medial prefrontal cortex in the rat produces events in midbrain dopaminergic neurons which resemble natural bursts, and which are closely time-locked to the stimulation, albeit with a very long latency. As a consequence, we have previously argued that such bursts are polysynaptically generated via more proximal excitatory amino acidergic afferents, arising, for example, from the pedunculopontine tegmental nucleus. In the present study, single-pulse electrical stimulation applied to this nucleus (and other sites in the rostral pons) was found to elicit responses in the majority of substantia nigra (A9) dopaminergic neurons. Responses usually consisted of long-latency, long-duration excitations or inhibition-excitations. Thirty-seven percent of responses (currents combined) elicited by stimulation of the pedunculopontine tegmental nucleus contained time-locked bursts, the bursts being embedded in the long-duration excitatory phases of excitation and inhibition-excitation responses. Stimulation sites located within 0.5 mm of the pedunculopontine tegmental nucleus were also effective at eliciting time-locked bursts (although less so than sites located in the nucleus itself), whereas more distal sites were virtually ineffective. For responses containing time-locked bursts, a higher percentage of stimulations produced a burst when the response was elicited from within the pedunculopontine tegmental nucleus than when it was elicited from outside: the bursts themselves having a very long latency (median of 96.2 ms; shorter than that of medial prefrontal cortex-induced bursts). Finally, although there was no difference in the distribution within the substantia nigra pars compacta of cells which exhibited time-locked bursting and those which did not, stimulation-induced bursts were elicited more frequently in dopaminergic neurons which were classified as "bursting" on the basis of their basal activity. The pedunculopontine tegmental nucleus appears to be a critical locus in the rostral pons for the elicitation of time-locked bursts in A9 dopaminergic neurons. Since time-locked bursts were more often elicited from cells which exhibited bursting under basal conditions, this suggests that rostral pontine sites, in particular the pedunculopontine tegmental nucleus, may play a role in the natural burst activity of dopaminergic neurons. Given that bursts in dopaminergic neurons are generated in response to primary and secondary reinforcers, the projection from the pedunculopontine tegmental nucleus could be one means by which motivationally relevant information (arising, for example, from the medial prefrontal cortex) reaches these cells.

Animals↗

Cardiac assessment with thallium scanning prior to aortic aneurysm repair.

Coronary artery disease occurs commonly in patients with aortic aneurysms and is a major cause of morbidity and mortality. The role of screening and intervention for cardiac disease prior to aneurysm repair is controversial. The outcome after cardiac screening with thallium scanning and/or angiography in 102 consecutive patients undergoing aortic aneurysm repair was documented. Significant coronary artery disease was found in 34 (33%) patients and two patients had either coronary artery bypass or angioplasty prior to aneurysm repair. There was no cardiac mortality after aneurysm repair and the overall mortality on an intention-to-treat basis was 2%. There was good correlation between prior history of cardiac events, electrocardiography (ECG) and the results of screening with thallium scanning and angiography. There was no correlation between cardiac history, ECG and the incidence of cardiac events in the postoperative period. Significant coronary artery disease was found in 33% of patients without a cardiac history or abnormal ECG. Cardiac screening with thallium scanning confirmed a high incidence of significant coronary disease in patients with aortic aneurysm. In this study, cardiac intervention followed by expedient aneurysm repair in 20 patients was associated with zero mortality. The short-term benefit of such a policy is difficult to prove and its main advantage may be better long-term survival.

Aged↗

A prospective study of routine antenatal enzyme antibody screening demonstrates lack of clinical value in predicting haemolytic disease of the newborn.

A prospective study of 7065 consecutive new pregnancies identified 230 with a positive screen, of which 27% (62/230) were 'enzyme-only' antibodies. 32 of these (52%) were potentially clinically important and were all of Rh specificity: 22 anti-E, seven anti-Cw, two anti-D and one anti-c. However, only three of these enzyme-only antibodies (one anti-D, one anti-c and one anti-E) became reactive by the indirect antiglobulin test (IAT) during the course of pregnancy, and all were detected in the routine 34-36-week maternal sample. No babies were affected, and we reaffirm that routine antibody screening by enzyme techniques is unnecessary.

Autoantibodies↗

Family and peer correlates of behavioral self-regulation in boys at risk for substance abuse.

Behavioral self-regulation (BSR), defined herein as the degree to which one can control one's own activity and reactivity to environmental stimuli, has been posited to be salient to the onset of adolescent substance abuse. The goal of this study was to clarify particular family and peer correlates of BSR in at-risk sons. Subjects were 10-through 12-year-old sons of substance-abusing fathers (high-average risk [HAR]; n = 176) and normal controls (low-average risk [LAR]; n = 199). A BSR latent trait was developed using multiple measures and multiple informants. Analyses included separate hierarchical linear regressions for HAR and LAR groups. In the hierarchical linear model for HAR sons, family dysfunction and deviant peer affiliation were significantly associated with BSR, whereas for LAR sons, only peer affiliation was significantly associated with BSR. The above family and peer correlates differed in proportions of variance explained for BSR in HAR and LAR sons. These findings extend previous studies by showing that, in a hierarchical linear model, BSR in HAR sons is associated with specific interpersonal, family, and peer factors. These findings suggest that empirical, theory-guided interventions to prevent worsening of BSR in HAR boys should address specific interpersonal, family, and peer factors.

Adult↗

From the decidual cell internet: trophoblast-recognizing T cells.

The mammalian fetus has been perceived, paradoxically, as a successful allograft, a successful tumor, and a successful parasite. Success depends on fetal trophoblast cells, which form the interface with the mother. The maternal immune system is involved in the success of pregnancy and in its failure. The discovery that maternal gammadelta T cells may recognize and react to the fetal trophoblast and the definition of a vascular mechanism whereby their Th1 and Th2/3-type cytokines may abort embryos replaces confusion and debate with a new and simple clarity that enables further research.

Animals↗

Pilot trial of infusional 5-fluorouracil, interleukin-2, and subcutaneous interferon-alpha for advanced renal cell carcinoma.

The authors developed an outpatient, three-drug combination regimen for advanced renal cell carcinoma. Treatment was administered for 5 days each week for 4 weeks, followed by 2-week rests. Each weekly treatment consisted of 5-fluorouracil 1,750 mg/m2 continuous intravenous infusion for 24 hours followed by interleukin-2 6 mIU/m2 per day continuous intravenous infusion for 4 days, and interferon-alpha2b 6 mU/m2 subcutaneously on days 1, 2, and 5. This trial was undertaken to assess tolerability to this regimen and obtain a preliminary assessment of its effectiveness. Most patients required some dose adjustments (especially of cytokines), treatment interruptions, or both. Toxicities were as would be expected from individual drug profiles with only mild to moderate hematologic toxicities. Among 16 patients with renal cell carcinoma treated, four had major (clinical partial response) responses, one of which was demonstrated to be a pathologic clinical response after surgical resection of a residual mass. Estimated median survival time of all patients was 93 weeks. Response and survival were correlated with known clinical risk factors. Responding patients were noted to be significantly older in age (X = 61.75 years) than nonresponders (X = 48.92 years). There was no correlation between age and other clinical risk factors, treatment tolerance, or survival. The authors conclude that this three-drug regimen is a practical, tolerable, and promising regimen for further study in renal cell carcinoma.

Adult↗