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Biomedical subjects

Karen L Smith

Publications and source records attributed to Karen L Smith.

16 recordsLinked to original sources
PubMed2026

Patient-reported outcomes from the TBCRC 022 study of neratinib and ado-trastuzumab emtansine for HER2-positive breast cancer brain metastases.

PURPOSE: In TBCRC 022 (NCT01494662), neratinib and ado-trastuzumab emtansine (T-DM1) demonstrated intracranial activity among patients with HER2-positive breast cancer brain metastases. However, gastrointestinal (GI) toxicities-particularly diarrhea-were common, potentially impacting quality of life. Clinician-reported adverse event (CTCAE) grading may underestimate the patient experience. We report GI toxicities using patient-reported outcomes (PROs) in TBCRC's neratinib-T-DM1 cohort. METHODS: Patients received neratinib (160&#x202f;mg daily) and T-DM1 (3.6&#x202f;mg/kg IV every 21 days). A pre-planned analysis assessed patient-reported GI toxicities during Cycles 1-4 using the Patient-reported Outcomes Measurement Information System (PROMIS) GI Diarrhea scale, Systemic Therapy-Induced Diarrhea Assessment Tool (STIDAT), and PRO-CTCAE. Descriptive statistics and linear mixed effects models evaluated symptom trajectories over time. We evaluated agreement for PRO and clinician-reported data. RESULTS: Forty-four patients enrolled; all completed &#x2265;1 PRO. GI symptom burden increased over Cycles 1-3. PROMIS scores worsened significantly by Cycle 2, with a peak mean increase of 6.62 (95% confidence interval (CI): 2.67-10.59; p&#x202f;=&#x202f;0.002) at Cycle 3. STIDAT scores also worsened by Cycle 3 (mean change 0.50; 95%CI: 0.11-0.90; p&#x202f;=&#x202f;0.015). Based on maximum PRO-CTCAE scores, moderate-to-severe symptoms were reported by 20.5% (diarrhea), 24.4% (appetite loss), and 41.0% (constipation). Agreement between PRO-CTCAE and clinician-reported CTCAE was low (kappa <0.2) with clinicians reporting less toxicity. PROMIS and STIDAT scores were significantly correlated. CONCLUSION: This GI-focused PRO analysis highlights the value of PROs in capturing patient-experienced toxicities that impact quality of life yet are underestimated by clinicians. Incorporating PROs into clinical trials can inform supportive care and prophylactic strategies.

Humans↗
PubMed2006

Low-density neuronal networks cultured using patterned poly-l-lysine on microelectrode arrays.

Synaptic activity recorded from low-density networks of cultured rat hippocampal neurons was monitored using microelectrode arrays (MEAs). Neuronal networks were patterned with poly-l-lysine (PLL) using microcontact printing (microCP). Polydimethysiloxane (PDMS) stamps were fabricated with relief structures resulting in patterns of 2 microm-wide lines for directing process growth and 20 microm-diameter circles for cell soma attachment. These circles were aligned to electrode sites. Different densities of neurons were plated in order to assess the minimal neuron density required for development of an active network. Spontaneous activity was observed at 10-14 days in networks using neuron densities as low as 200 cells/mm(2). Immunocytochemistry demonstrated the distribution of dendrites along the lines and the location of foci of the presynaptic protein, synaptophysin, on neuron somas and dendrites. Scanning electron microscopy demonstrated that single fluorescent tracks contained multiple processes. Evoked responses of selected portions of the networks were produced by stimulation of specific electrode sites. In addition, the neuronal excitability of the network was increased by the bath application of high K(+) (10-12 mM). Application of DNQX, an AMPA antagonist, blocked all spontaneous activity, suggesting that the activity is excitatory and mediated through glutamate receptors.

Action Potentials↗
PubMed2005

Automated image analysis methods for 3-D quantification of the neurovascular unit from multichannel confocal microscope images.

BACKGROUND: There is a need for integrative and quantitative methods to investigate the structural and functional relations among elements of complex systems, such as the neurovascular unit (NVU), that involve multiple cell types, microvasculatures, and various genomic/proteomic/ionic functional entities. METHODS: Vascular casting and selective labeling enabled simultaneous three-dimensional imaging of the microvasculature, cell nuclei, and cytoplasmic stains. Multidimensional segmentation was achieved by (i) bleed-through removal and attenuation correction; (ii) independent segmentation and morphometry for each corrected channel; and (iii) spatially associative feature computation across channels. The combined measurements enabled cell classification based on nuclear morphometry, cytoplasmic signals, and distance from vascular elements. Specific spatial relations among the NVU elements could be quantified. RESULTS: A software system combining nuclear and vessel segmentation codes and associative features was constructed and validated. Biological variability contributed to misidentified nuclei (9.3%), undersegmentation of nuclei (3.7%), hypersegmentation of nuclei (14%), and missed nuclei (4.7%). Microvessel segmentation errors occurred rarely, mainly due to nonuniform lumen staining. CONCLUSIONS: Associative features across fluorescence channels, in combination with standard features, enable integrative structural and functional analysis of the NVU. By labeling additional structural and functional entities, this method can be scaled up to larger-scale systems biology studies that integrate spatial and molecular information.

Animals↗
PubMed2005

Prehospital prediction of intensive care unit stay and mortality in blunt trauma patients.

BACKGROUND: The success of a trauma system relies on transfer of patients from the field to the most appropriate hospital for definitive care. However, no consensus has been reached regarding the best criteria or triage tool for identifying patients injured seriously enough to warrant transfer to a trauma center. METHODS: Predictors of mortality and intensive care unit stay were identified and prediction models developed in a design data set. The performance of these models was evaluated in a test data set and compared with current trauma triage guidelines, derived from the American College of Surgeons model. RESULTS: The newly developed prediction models performed comparably with the current trauma triage guidelines. CONCLUSION: Although the performance of newly developed triage models was promising, their performance did not exceed that of the current trauma triage guidelines. In particular, the anatomic injury criteria appeared to be the key component of the current trauma triage guidelines.

Decision Support Techniques↗
PubMed2005

The trauma registry as a statewide quality improvement tool.

BACKGROUND: Trauma registries have been developed to describe the pattern of trauma and trauma workload, provide data for research, and to demonstrate changes in patient outcomes. Quality improvement using trauma registries at a system-wide level has been difficult to achieve. In Victoria, Australia, a statewide trauma system and trauma registry has been established to monitor and feedback the process of management and outcomes of major trauma patients across all healthcare providers. METHODS: The development and implementation of the Victorian State Trauma Registry (VSTR), including its role as a quality monitoring tool and results from the first 2 years of operation, are provided. RESULTS: More than 80% of major trauma patients are being managed at major trauma services and standardized death rates are comparable with international standards. Quality indicators identify some areas for improvement. CONCLUSION: VSTR data indicate that the statewide trauma system is working well and provides a method for ongoing monitoring and trauma care feedback.

Adolescent↗
PubMed2005

Predictors of mortality, length of stay and discharge destination in blunt trauma.

BACKGROUND: The present study explored a range of variables to identify predictors of mortality and morbidity and to develop prediction models based on these variables. METHODS: Tools for predicting mortality, hospital length of stay and a patient's destination post-hospital discharge were developed using logistic regression in one dataset (design) and evaluated for prediction performance in a separate dataset (validation). The performance of the mortality model was compared to the trauma and injury severity score (TRISS) and a severity characterization of trauma (ASCOT). RESULTS: The profile of variables contributing to the final prediction models developed from the design dataset varied across the different outcomes of interest although age, injury severity score, development of complications and triage category were common predictors of all three outcomes. The performance of the new mortality prediction model was superior to both TRISS and ASCOT in the validation dataset. Overall, the new models did not meet the prespecified performance criteria. CONCLUSIONS: The present study identified key predictors of mortality and morbidity (length of hospital stay and discharge destination). The newly developed mortality model out-performed published trauma scoring methods. However, further development and trial of the new prediction models is required before implementation as definitive audit and benchmarking tools could be recommended.

Adult↗
PubMed2004

Extracellular recordings from patterned neuronal networks using planar microelectrode arrays.

Neuronal cell networks have been reconstructed on planar microelectrode arrays (MEAs) from dissociated hippocampal pyramidal neurons. Microcontact printing (microCP) and a photoresist-liftoff method were used to selectively localize poly-L-lysine (PLL) on the surface of MEAs. Haptotaxis led to the organization of the neurons into networks localized adjacent to microelectrodes. Various grids of PLL with 2-25-microm-wide lines spaced by 50-200 microm with 15-25-microm nodes at intersection points were used to guide cell body attachment and neurite outgrowth. Bursting activity with spike amplitude attenuation was observed, and multichannel recordings detected instances of coincident firing activity. Finally, we present here an extracellular recording from a approximately 2 microm bundle of guided neurites.

Action Potentials↗
PubMed2004

Model neural prostheses with integrated microfluidics: a potential intervention strategy for controlling reactive cell and tissue responses.

Model silicon intracortical probes with microfluidic channels were fabricated and tested to examine the feasibility of using diffusion-mediated delivery to deliver therapeutic agents into the volume of tissue exhibiting reactive responses to implanted devices. Three-dimensional probe structures with microfluidic channels were fabricated using surface micromachining and deep reactive ion etching (DRIE) techniques. In vitro functional tests of devices were performed using fluorescence microscopy to record the transient release of Texas Red labeled transferrin (TR-transferrin) and dextran (TR-dextran) from the microchannels into 1% w/v agarose gel. In vivo performance was characterized by inserting devices loaded with TR-transferrin into the premotor cortex of adult male rats. Brain sections were imaged using confocal microscopy. Diffusion of TR-transferrin into the extracellular space and uptake by cells up to 400 microm from the implantation site was observed in brain slices taken 1 h postinsertion. The reactive tissue volume, as indicated by the presence of phosphorylated mitogen-activated protein kinases (MAPKs), was characterized using immunohistochemistry and confocal microscopy. The reactive tissue volume extended 600, 800, and 400 microm radially from the implantation site at 1 h, 24 h, and 6 weeks following insertion, respectively. These results indicate that diffusion-mediated delivery can be part of an effective intervention strategy for the treatment of reactive tissue responses around chronically implanted intracortical probes.

Animals↗
PubMed2004

Developing Australia's first statewide trauma registry: what are the lessons?

Trauma registries, like disease registries, provide an important analysis tool to assess the management of patient care. Trauma registries are well established and relatively common in the USA and have been used to change legislation, promote trauma prevention and to evaluate trauma system effectiveness. In Australia, the first truly statewide trauma registry was established in Victoria in 2001 with an estimated capture of 1700 major trauma cases annually. The Victorian State Trauma Registry, managed by the Victorian State Trauma Outcomes Registry and Monitoring (VSTORM) group, was established in response to a ministerial review of trauma and emergency services undertaken in 1997 to advise the Victorian Government on a best practice model of trauma service provision that was responsive to the particular needs of critically ill trauma patients. This taskforce recommended the establishment of a new system of care for major trauma patients in Victoria and a statewide trauma registry to monitor this new system. The development of the Victorian state trauma registry has shown that there are certain issues that must be resolved for successful implementation of any system-wide registry. This paper describes the issues faced by VSTORM in developing, implementing and maintaining a statewide trauma registry.

Australia↗
PubMed2003

C-reactive protein, Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus and risk for myocardial infarction.

PURPOSE: C-reactive protein (CRP), Chlamydia pneumonia, Helicobacter pylori, and cytomegalovirus (CMV) have each been associated with atherosclerosis. We assessed how infection and CRP related to risk for subsequent myocardial infarction (MI). METHODS: Using a nested case-control design, we assessed how these factors independently and jointly affected risk for myocardial infarction (MI). Cases of first MI (N = 121) were identified from among participants in a multiphasic health check-up cohort. Controls without MI (N = 204) were matched to cases by gender, age, race, and date of serum collection. Sera collected at enrollment were tested for antibodies to infection and for CRP. RESULTS: In multivariate analysis (mean follow-up of 5.1 years), CRP was associated with MI only in subjects older than 51 years (p = 0.004). Although H. pylori infection increased risk for MI, this association was modest (OR = 1.90, 95% CI = 0.97-3.71) and was not evident in non-smokers or when adjusted for education. No association between C. pneumoniae or cytomegalovirus and MI was observed, nor was the association between CRP and MI explained by these infections. CONCLUSIONS: Elevated CRP is a risk factor for subsequent MI in older individuals. The relationship between Hp and MI may be due to confounding or co-linearity with socioeconomic status.

Adult↗
PubMed2002

Structural and functional asymmetry in the normal and epileptic rat dentate gyrus.

The rat dentate gyrus is usually described as relatively homogeneous. Here, we present anatomic and physiological data which demonstrate that there are striking differences between the supra- and infrapyramidal blades after status epilepticus and recurrent seizures. These differences appear to be an accentuation of a subtle asymmetry present in normal rats. In both pilocarpine and kainic acid models, there was greater mossy fiber sprouting in the infrapyramidal blade. This occurred primarily in the middle third of the hippocampus. Asymmetric sprouting was evident both with Timm stain as well as antisera to brain-derived neurotrophic factor (BDNF) or neuropeptide Y (NPY). In addition, surviving NPY-immunoreactive hilar neurons were distributed preferentially in the suprapyramidal region of the hilus. Extracellular recordings from infrapyramidal sites in hippocampal slices of pilocarpine-treated rats showed larger population spikes and weaker paired-pulse inhibition in response to perforant path stimulation relative to suprapyramidal recordings. A single stimulus could evoke burst discharges in infrapyramidal granule cells but not suprapyramidal blade neurons. BDNF exposure led to spontaneous epileptiform discharges that were larger in amplitude and longer lasting in the infrapyramidal blade. Stimulation of the infrapyramidal molecular layer evoked larger responses in area CA3 than suprapyramidal stimulation. In slices from the temporal pole, in which anatomic evidence of asymmetry waned, there was little evidence of physiological asymmetry either. Of interest, some normal rats also showed signs of greater evoked responses in the infrapyramidal blade, and this could be detected with both microelectrode recording and optical imaging techniques. Although there were no signs of hyperexcitability in normal rats, the data suggest that there is some asymmetry in the normal dentate gyrus and this asymmetry is enhanced by seizures. Taken together, the results suggest that supra- and infrapyramidal blades of the dentate gyrus could have different circuit functions and that the infrapyramidal blade may play a greater role in activating the hippocampus.

Animals↗
PubMed2002

Cardiac arrests treated by ambulance paramedics and fire fighters.

The Emergency Medical Response (EMR) program is a Victorian Government initiative in which fire fighters trained in cardiopulmonary resuscitation and equipped with automatic external defibrillators are dispatched to suspected cardiac arrests simultaneously with ambulance paramedics across metropolitan Melbourne. During the first 12 months (February 2000 to February 2001) of the expanded EMR program, 2942 events involved simultaneous dispatch of ambulance paramedics and fire fighters. In 430 events, patients had suffered a cardiac arrest of presumed cardiac cause, and resuscitation was attempted by the emergency medical services. Fire fighters provided the initial defibrillation to 41 (26.5%) patients presenting in ventricular fibrillation. Survival to hospital discharge for bystander-witnessed ventricular fibrillation cardiac arrests was 21.8%. The mean emergency services (fire and ambulance) response time to cardiac arrest patients was 6.03 (SD, 1.65) minutes. The mean time to defibrillation for ventricular fibrillation patients was 8.75 (SD, 2.07) minutes.

Cardiopulmonary Resuscitation↗
PubMed2002

Rapid assessment of marine pollution using multiple biomarkers and chemical immunoassays.

To fully assess the impact of pollutant releases into the environment, it is necessary to determine both the concentration of chemicals accumulating in biota and the biological effects they give rise to. Owing to time, expertise, and cost constraints, this is, however, rarely achieved. Here, quick, simple to perform, and inexpensive biomarkers and chemical immunoassays were combined in a rapid assessment approach to measure exposure to and effects of organic and metal pollutants on the ribbed mussel (Geukensia demmissa) from New Bedford Harbor, MA. Significant differences in polychlorinated biphenyl (PCB) and polyaromatic hydrocarbon (PAH) tissue residue concentrations were detected among sites using RaPID immunoassay. Selected analyses were verified using GC/MS. No significant differences were observed in metal concentrations (Cu, Cd, Pb, As, Hg, Ni) throughout the area. While causality cannot be attributed, multivariate canonical correlation analysis indicated that PCB and PAH concentrations were strongly associated with the induction of biomarkers of genotoxicity (micronucleus formation), immunotoxicity (spontaneous cytotoxicity), and physiological impairment (heart rate). It is concluded thatthe incorporation of chemical immunoassays with biological monitoring tools into routine management procedures is clearly viable and valuable as a means of identifying toxic impacts of pollutants on biota in situ.

Animals↗
PubMed2002

Does catheter type effect pregnancy rate in intrauterine insemination cycles?

PURPOSE: To determine if a soft insemination catheter increases pregnancy rates. METHODS: Seven hundred forty-seven consecutive intrauterine insemination (IUI) cycles in 364 women in a reproductive endocrinology office between October 1998 and March 2000. Patients with even birth years were inseminated with the Tomcat catheter, and those with odd birth year with the Wallace IUI catheter. Clinical pregnancy rates were compared. RESULTS: The Wallace catheter group included 180 women for 372 cycles and an overall pregnancy rate of 16.4%. The Tomcat catheter group included 184 women for 375 cycles and an overall pregnancy rate of 18.1%. This difference is not statistically significant (P = 0.61). Potential confounders were accounted for. CONCLUSIONS: When comparing the softer Wallace catheter to the less pliable Tomcat catheter during IUI cycles, there was no significant difference in pregnancy rate when using a standard gentle technique that includes not touching the top of the fundus with the catheter.

Adult↗
PubMed2002

Knowledge of heart attack symptoms in a community survey of Victoria.

OBJECTIVE: To ascertain the level of knowledge of heart attack symptoms in the Victorian public. METHODS: This was a cross sectional telephone survey conducted during 2000-01. The questionnaire contained sections regarding participant demographics and knowledge of heart attack symptoms. RESULTS: A total of 1489 people completed the questionnaire (79% of eligible participants). The mean number of correct heart attack symptoms was 2.5 (95% CI 2.45, 2.60) (median three out of 10). Only 4.2% of participants reported at least five correct symptoms and 4.1% could not report any symptoms. A total of 84.6% of respondents reported chest pain as a symptom of heart attack. CONCLUSIONS: The Victorian public appears to lack the knowledge of the varied range of heart attack symptoms. Methods of disseminating information regarding symptoms and ways to reduce prehospital delay need to be devised, particularly methods which target the older 'at risk' population.

Adult↗