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Biomedical subjects

C Russell

Publications and source records attributed to C Russell.

At least 19 recordsLinked to original sources

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials.

Gastrin has been shown to be a growth stimulant in pancreatic cancer cells. Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised blinded trials were conducted to assess the effect of gastrazole in advanced pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5-FU). Eighteen patients were randomised in trial A. Gastrazole produced significantly better survival compared to placebo (median 7.9 months vs 4.5 months; 1-year survival: 33 vs 11%, respectively; log rank P=0.02). No difference in toxicity was seen between gastrazole and placebo, except central venous catheter and pump complications. Ninety-eight patients were randomised in trial B. No significant survival difference was detected between gastrazole and 5-FU (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log rank P=0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P=0.03), stomatitis (P<0.001) and hand- foot syndrome (P<0.001) compared to 5-FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5-FU at baseline and no significant differences occurred with treatment either between arms or within arms. Compared to placebo, patients with advanced pancreatic cancer treated with gastrazole appeared to live longer, albeit in a very small trial and will require confirmation with large-scale randomised data. However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity for gastrazole may allow its combination with cytotoxic drugs.

Adult↗

ATVs: motorized toys or vehicles for children?

OBJECTIVES: To compare the nature of injuries from all-terrain vehicles (ATVs) to those from bicycling, dirtbikes/motocross, and motor vehicle crashes. DESIGN: Data on injuries from the mechanisms outlined above were obtained through CHIRPP (the Canadian Hospitals Injury Reporting and Prevention Program) and hospital records. SETTING: A Canadian tertiary pediatric center. SUBJECTS: Cases presenting to the emergency department over a 10 year period. MAIN OUTCOME MEASURES: Comparison between demographics, mechanisms and natures of injuries sustained, disposition from the emergency department, and lengths of hospital stay. RESULTS: Contrary to bicycling, ATV related injuries occurred among older ages and appeared to result less often from loss of control. Severe injuries resulting in deep soft tissue trauma and fracture/dislocations were 1.7 and 1.5 times, respectively, more frequent among ATV trauma than bicycling (p<0.01). In addition, ATV related injuries were located more frequently in the trunkal, hip, lower extremity, and spinal regions. Conversely, ATV related trauma bore significant similarities regarding body part and nature of the injury to both motor vehicle crash (MVC) and dirtbike related injuries. Akin to dirtbike and MVC related trauma, ATV related injuries more frequently required admission to the ward or intensive care unit compared to bicycling injuries (30.8% v 9.6%, p<0.0001), and used a proportionally larger amount of hospital resources with respect to overall in-hospital and intensive care unit days. CONCLUSIONS: Although ATVs may be considered recreational for children, their associated injury patterns, severity, and costs to the healthcare system more closely resemble those from motorized vehicles and are more significant than bicycling. Strict policy to reflect this must be developed and acknowledged by the public, industry, and legislative bodies.

Accidents↗

Ethicists and clinicans: the case for collaboration in the teaching of medical ethics.

It has become part of conventional wisdom that medical students experience a clear separation between the explicit ethics curriculum of the lecture room and the implicit curriculum of the clinic. This paper outlines and critiques some important assumptions made about the teaching of ethics in medical schools. It identifies the need for close collaboration between clinical and non-medical ethics teachers to advance the teaching of ethics in medical training.

Cooperative Behavior↗

Spatial dynamics and molecular ecology of North American rabies.

Rabies, caused by a single-stranded RNA virus, is arguably the most important viral zoonotic disease worldwide. Although endemic throughout many regions for millennia, rabies is also undergoing epidemic expansion, often quite rapid, among wildlife populations across regions of Europe and North America. A current rabies epizootic in North America is largely attributable to the accidental introduction of a particularly well-adapted virus variant into a naive raccoon population along the Virginia/West Virginia border in the mid-1970s. We have used the extant database on the spatial and temporal occurrence of rabid raccoons across the eastern United States to construct predictive models of disease spread and have tied patterns of emergence to local environmental variables, genetic heterogeneity, and host specificity. Rabies will continue to be a remarkable model system for exploring basic issues in the temporal and spatial dynamics of expanding infectious diseases and examining ties between disease population ecology and evolutionary genetics at both micro- and macro-evolutionary time scales.

Algorithms↗

Effects of the PKC inhibitor PD 406976 on cell cycle progression, proliferation, PKC isozymes and apoptosis in glioma and SVG-transformed glial cells.

It is well established that protein kinase C (PKC) isozymes are involved in the proliferation of glioma cells. However, reports differ on which PKC isozymes are responsible for glioma proliferation. As a means to further elucidate this, the objectives of our research were to determine how inhibition of PKC-alpha, PKC-beta and PKCmu with PD 406976 regulates the cell cycle, cell proliferation and PKC during glioma growth and development. To establish the cell cycle effects of PD 406976 on brain cells (SVG, U-138MG and U-373MG glioma cells), specimens were treated with either dimethylsulfoxide (DMSO; control) or PD 406976 (2 microm). Results from flow cytometry demonstrated that PD 406976 delayed the entry DNA synthesis phase in SVG cells and delayed the number of cells entering and exiting the DNA synthesis phase in both U-138MG and U-373MG cells, indicating that PD 406976 may inhibit G(1)/S and S phase progression. Assessment of cell viability demonstrated a cytostatic effect of PD 406976 on SVG, U-138MG and U-373MG glioma cell proliferation. The PD 406976-induced decreased proliferation was sustained at 48-96 h. A PKC activity assay was quantified and demonstrated that exposure of SVG and U-373MG glioma cells to PD 406976 suppressed PKC activity. Western blotting demonstrated reduced PKC-beta1, PKC-gamma and PKC-tau protein content in cells treated with PD 406976. We determined that the growth inhibitory effect of PD 406976 was not as a result of apoptosis.

Apoptosis↗

Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos.

Serotonin (5HT) plays major roles in the physiological regulation of many behavioral processes, including sleep, feeding, and mood, but the genetic mechanisms by which serotonergic neurons arise during development are poorly understood. In the present study, we have investigated the development of serotonergic neurons in the zebrafish. Neurons exhibiting 5HT-immunoreactivity (5HT-IR) are detected from 45 h postfertilization (hpf) in the ventral hindbrain raphe, the hypothalamus, pineal organ, and pretectal area. Tryptophan hydroxylases encode rate-limiting enzymes that function in the synthesis of 5HT. As part of this study, we cloned and analyzed a novel zebrafish tph gene named tphR. Unlike two other zebrafish tph genes (tphD1 and tphD2), tphR is expressed in serotonergic raphe neurons, similar to tph genes in mammalian species. tphR is also expressed in the pineal organ where it is likely to be involved in the pathway leading to synthesis of melatonin. To better understand the signaling pathways involved in the induction of the serotonergic phenotype, we analyzed tphR expression and 5HT-IR in embryos in which either Hh or Fgf signals are abrogated. Hindbrain 5HT neurons are severely reduced in mutants lacking activity of either Ace/Fgf8 or the transcription factor Noi/Pax2.1, which regulates expression of ace/fgf8, and probably other genes encoding signaling proteins. Similarly, serotonergic raphe neurons are absent in embryos lacking Hh activity confirming a conserved role for Hh signals in the induction of these cells. Conversely, over-activation of the Hh pathway increases the number of serotonergic neurons. As in mammals, our results are consistent with the transcription factors Nk2.2 and Gata3 acting downstream of Hh activity in the development of serotonergic raphe neurons. Our results show that the pathways involved in induction of hindbrain serotonergic neurons are likely to be conserved in all vertebrates and help establish the zebrafish as a model system to study this important neuronal class.

Animals↗

Removal of ocular artifacts from electro-encephalogram by adaptive filtering.

The electro-encephalogram (EEG) is useful for clinical diagnosis and in biomedical research. EEG signals, however, especially those recorded from frontal channels, often contain strong electro-oculogram (EOG) artifacts produced by eye movements. Existing regression-based methods for removing EOG artifacts require various procedures for preprocessing and calibration that are inconvenient and time-consuming. The paper describes a method for removing ocular artifacts based on adaptive filtering. The method uses separately recorded vertical EOG and horizontal EOG signals as two reference inputs. Each reference input is first processed by a finite impulse response filter of length M (M = 3 in this application) and then subtracted from the original EEG. The method is implemented by a recursive least-squares algorithm that includes a forgetting factor (lambda = 0.9999 in this application) to track the non-stationary portion of the EOG signals. Results from experimental data demonstrate that the method is easy to implement and stable, converges fast and is suitable for on-line removal of EOG artifacts. The first three coefficients (up to M = 3) were significantly larger than any remaining coefficients.

Algorithms↗

Adcon -L gel and intraoperative hypotension during lumbar discectomy.

This case report describes an intraoperative hypotensive event associated temporally with application of topical Adcon -L gel during lumbar surgery. Documented serum cardiac and immunological markers suggest a non-anaphylactoid aetiology. The aetiology of this phenomenon is discussed with reference to available literature.

Aged↗

A cohort study of early neurological consultation by telemedicine on the care of neurological inpatients.

OBJECTIVES: To find out the effect of early neurological consultation using a real time video link on the care of patients with neurological symptoms admitted to hospitals without neurologists on site. METHODS: A cohort study was performed in two small rural hospitals: Tyrone County Hospital (TCH), Omagh, and Erne Hospital, Enniskillen. All patients over 12 years of age who had been admitted because of neurological symptoms, over a 24 week period, to either hospital were studied. Patients admitted to TCH, in addition to receiving usual care, were offered a neurological consultation with a neurologist 120 km away at the Neurology Department of the Royal Victoria Hospital, Belfast, using a real time video link. The main outcome measure was length of hospital stay; change of diagnosis, mortality at 3 months, inpatient investigation, and transfer rate and use of healthcare resources within 3 months of admission were also studied. RESULTS: Hospital stay was significantly shorter for those admitted to TCH (hazard ratio 1.13; approximate 95% CI 1.003 to 1.282; p = 0.045). No patients diagnosed by the neurologist using the video link subsequently had their diagnosis changed at follow up. There was no difference in overall mortality between the groups. There were no differences in the use of inpatient hospital resources and medical services in the follow up period between TCH and Erne patients. CONCLUSIONS: Early neurological assessment reduces hospital stay for patients with neurological conditions outside of neurological centres. This can be achieved safely at a distance using a real time video link.

Adult↗

Development of an assessment tool to measure the influence of clinical software on the delivery of high quality consultations. A study comparing two computerized medical record systems in a nurse run heart clinic in a general practice setting.

A rating scale was developed to assess the contribution made by computer software towards the delivery of a quality consultation, with the purpose of informing the development of the next generation of systems. Two software programmes were compared, using this scale to test their ability to enable or inhibit the delivery of an ideal consultation with a patient with heart disease. The context was a general practice based, nurse run clinic for the secondary prevention of heart disease. One of the programmes was customized for this purpose; the other was a standard general practice programme. Consultations were video-recorded, and then assessed by an expert panel using the new assessment tool. Both software programmes were oriented towards the implementation of the evidence, rather than facilitating patient-centred practice. The rating scale showed, not surprisingly, significantly greater support from the customized software in the consultation in five out of eight areas. However, the scale's reliability measured by Cronbach's Alpha, was sub-optimal. With further refinement, this rating scale may become a useful tool that will inform software developers of the effectiveness of their programmes in the consultation, and suggest where they need development.

Ambulatory Care↗

Follow-up of a large cohort of Black women.

High retention rates in follow-up studies reduce the potential for biased data due to selective losses. The Black Women's Health Study began in 1995 when 64,500 participants aged 21-69 years enrolled by completing postal health questionnaires. Follow-up is carried out biennially. On the basis of data collected between enrollment and completion of the first follow-up, the authors assessed the usefulness of various follow-up methods and compared the characteristics of respondents, nonrespondents, and women lost to follow-up because of an unknown address. The 1997 questionnaire was completed by 82.8% of the participants. The study population was highly mobile: 56.5% moved at least once, and 1.5% moved at least four times. Moving was associated with younger age: A total of 71.7% of participants aged 21-29 years moved at least once compared with 43.2% of women aged 50-69. The most successful and cost-effective method for eliciting completed questionnaires from participants was sending multiple waves of questionnaires. Telephone calls to nonrespondents were successful but were highly labor intensive. Demographic and health characteristics of the women were similar regardless of which mailing was completed, except that early respondents had higher levels of education. Respondents were more highly educated and older than were nonrespondents and lost subjects but were quite similar in all other characteristics. These data suggest that follow-up of a mobile population of African-American women can be successful.

Adult↗

Segmentation, attention and phenomenal visual objects.

Issues concerning selective attention provoke new questions about visual segmentation, and vice-versa. We illustrate this by describing our recent work on grouping under conditions of inattention, on change blindness for background events and the residual processing of undetected background changes, on modal versus amodal completion in visual search, and the differential effects of these two forms of completion on attentional processes, and on attentional modulation of lateral interactions thought to arise in early visual cortex. Many of these results indicate that segmentation processes substantially constrain attentional processes, but the reverse influence is also apparent, suggesting an interactive architecture. We discuss how the 'proto-objects' revealed by studies of segmentation and attention (i.e. the segmented perceptual units which constrain selectivity) may relate to other object-based notions in cognitive science, and we wrestle with their relation to phenomenal visual awareness.

Attention↗

Critical analysis of everyday self-care decision making in chronic illness.

AIMS OF THE PAPER: The purpose of the paper is to (1) identify prevalent assumptions that underlie the traditional conceptualization of everyday self-care decision making and (2) contrast these with the findings of relevant research. BACKGROUND/RATIONALE: Current understandings of self-care decision making in chronic illness tend to be extrapolated from knowledge gained in relation to one-time decisions, or decision making in contexts that are only superficially related to the complexity and pervasiveness of living with a chronic disease. FINDINGS: The authors challenge the assumptions with which current understandings represent self-care decision making in chronic illness, using evidence from their research on what it is like to live with and manage the implications of having a chronic disease on an everyday basis. CONCLUSIONS: The paper concludes with a call for a new conceptualization of self-care decision making in chronic illness which sufficiently addresses the unique and complex nature of such decisions.

Adaptation, Psychological↗

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine.

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.

Adult↗

Home enteral tube feeding following cerebrovascular accident.

BACKGROUND AND AIMS: In the UK, cerebrovascular accident (CVA) is the third commonest cause of death and the commonest diagnosis in patients receiving home enteral feeding (HETF). This study aimed to use data from the British Artificial Nutrition Survey (BANS) collected between 1996 and 1999 to assess the outcome of patients on HETF, including mortality, return to oral feeding, level of physical activity, and level of dependency, which has resource implications. RESULTS: it is estimated that about 1.7% of all patients suffering a CVA in the UK between 1996 and 1999 received HETF. At one year, 29.6% died while receiving HETF and another 13% returned to oral feeding. Mortality increased with age and was twice as high in those managed in nursing homes compared to those in their own homes. The patients receiving tube feeding spent only 0.6% of their time in hospital. A total of 43.9% of patients were bed-bound at home (1.9% unconscious) and an additional 30.3% were house-bound. Only 21.2% were independent, and the majority were totally dependent on their carers. In CVA patients on HETF the level of dependency was greater than for those with all types of diagnoses (n=12,997). CONCLUSION: This study has described the outcome of a large number of patients receiving HETF in the UK. Since patients spent less than 1% of their time in hospital, HETF relieves pressure on the expensive hospital environment, but places more demands on the carers, who have to deal with severely disabled patients. Recovery of swallowing function should be assessed intermittently to prevent unnecessary HETF.

Adolescent↗