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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 55 records · Page 3Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

'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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

Environmental health officers' understanding about an aboriginal environmental health worker program in the Northern Territory.

OBJECTIVE: To explore environmental health officers' (EHOs) perception that a program to train Aboriginal people as environmental health workers in 10 remote Northern Territory communities was not operating well. METHOD: Phenomenography, an approach within the qualitative domain, was used to explore 15 EHOs' understanding about the program during 1996-97. Respondents came from four of the Territory's five operational districts. RESULTS: Respondents were unclear about worker roles and responsibilities within the program. Perceptions about their own skills as trainers in a cross-cultural context inhibited their abilities to support the program effectively. CONCLUSIONS: Addressing the support, orientation and professional development needs of EHOs will enhance program effectiveness. IMPLICATIONS: Support staff should be adequately prepared and trained before a new program is commenced.

Allied Health Personnel↗
PubMed1999

Molecular mapping of chromosome 2 deletions in murine radiation-induced AML localizes a putative tumor suppressor gene to a 1.0 cM region homologous to human chromosome segment 11p11-12.

Radiation-induced acute myeloid leukemias (AMLs) in the mouse are characterized by chromosome 2 deletions. Previous studies showed that a minimal deleted region (mdr) of approximately 6.5 cM is lost from one homologue in chromosome 2-deleted AMLs. An AML tumor suppressor gene is proposed to map within this mdr. In this study, we refine the mdr to a I cM interval between markers D2Mit126 and D2Mit185 by microsatellite analysis of 21 primary radiation-induced F I AMLs. The construction of a partial yeast artificial chromosome (YAC) contig spanning the mdr and the location of six known genes indicated that the 1 cM mdr is homologous to human 11p11-12, a region implicated in some human AMLs. Screening of five cell lines derived from primary radiation-induced AMLs for homozygous loss of microsatellites and genes mapping within the mdr revealed loss of both copies of the hemopoietic tissue-specific transcription factor Sfpi1(PU.1/Spi1) in one cell line. Studies of primary and F1 AMLs failed to implicate Sfpi1 as the AML tumor suppressor gene. YAC contig construction, together with data suggesting that the critical gene flanks Sfpi1, represents significant progress toward identifying an AML tumor suppressor gene.

Animals↗
PubMed1998

Perturbation of nucleosome structure by the erythroid transcription factor GATA-1.

The ability of transcription factors to gain access to their sites in chromatin requires the disruption or displacement of nucleosomes covering the promoter, signalled by the generation of a nuclease hypersensitive site. We characterise here the alterations in nucleosome structure caused by binding of the erythroid factor GATA-1 to a nucleosome carrying GATA-1 sites. DNase I and micrococcal nuclease probes show that GATA-1 binding causes extensive, cooperative breakage of the histone/DNA contacts to generate a complex very similar to that formed by the factor with free DNA. The only region which differs is confined to about 50 bp surrounding the nucleosome dyad axis which appears to be the domain of residual contact between the DNA and histone octamer. Despite considerable breakage of the histone/DNA contacts, the complex is completely stable in solution, and disruption of the nucleosome is entirely reversible: it is regenerated quantitatively upon removal of the transcription factor. Moreover, the histone 2A/2B component of the octamer does not exchange to external competitor. We suggest that formation of this complex may be a step in the generation of a fully hypersensitive site in vivo over regulatory elements containing GATA family binding sites.

Animals↗