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Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 37 records · Page 2Linked to original sources
PubMed2004

A model for cardiopulmonary bypass redesign.

INTRODUCTION: A portion of patients undergoing cardiac surgery may develop focal and/or subtle brain injuries secondary to cardiac surgery. There is evidence that, in some cases, these injuries may be related to cardiopulmonary bypass (CPB). Embolism and hypoperfusion are the dominant mechanisms for focal neurologic injuries among coronary artery bypass graft (CABG) surgery patients. Recent studies suggest that these mechanisms may also produce the more prevalent subtle neurological deficits. The aim of our current work is to obtain a thorough understanding of the processes of care associated with the production of embolic activity, cerebral hypoperfusion, and hemodynamic aberrations that often occur during CPB. METHODS: We developed a system for simultaneous recording of physiologic parameters, embolic activity in the CPB circuit and in the cerebral arteries, and near infrared regional cerebral oxyhemoglobin saturation (NIRS) during cardiac surgery. All data were synchronized with a video recording of the surgical procedure. Periods of embolic activity and NIRS were subsequently related to surgical and CPB processes of care through a systematic review of the patient's surgical case video. RESULTS: To date, we have enrolled 47 patients undergoing coronary and/or valvular procedures. We have observed wide variation across patients in detected cerebral embolic counts, NIRS and physiologic parameters. We have identified increased embolic counts in the CPB circuit related to specific processes and events such as the method of venous drainage, the entrainment of air in the venous line, the injection of medications into the CPB circuit and blood sampling from the CPB circuit. A portion of detected changes in NIRS were related to periods of hypotension and positioning of the heart during the construction of distal coronary artery grafts on the posterior coronary artery vessels. SUMMARY: Use of this model provides the surgical team with detailed information regarding the contribution of CPB to the creation of precursors of neurological injury. This system provides meaningful data to guide the surgical team in the redesign of the CPB system and associated techniques.

Brain Injuries↗
PubMed2003

CYP3A4 and VDR gene polymorphisms and the risk of prostate cancer in men with benign prostate hyperplasia.

Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. The vitamin D receptor (VDR) and CYP3A4 have been shown to be involved in the regulation of cell proliferation and differentiation in prostate cells. Genetic variations of these genes have been associated with PRCa in case-control studies and may be useful to detect BPH patients that have a higher risk of developing PRCa. The association between CYP3A4 and VDR TaqI SNPs and the risk of developing PRCa have been investigated in this study by determining the variant genotype frequencies of both SNPs in 400 patients with BPH who have been followed clinically for a median of 11 years. The results of this study showed that the incidence rate of PRCa was higher in BPH patients having CYP3A4 variant genotype compared to those with wild type (relative risk (RR)=2.7; 95% CI=0.77-7.66). No association between variant genotype and risk of developing PRCa was observed with the VDR TaqI variant genotype. In addition, the results of combined genotype analysis of these two SNPs showed a borderline significant association between CYP3A4 and VDR TaqI combined variant genotypes and PRCa risk (RR=3.43; 95% CI=0.99-11.77). While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease.

Case-Control Studies↗
PubMed2003

Cu, Cr and As distribution in soils adjacent to pressure-treated decks, fences and poles.

Chromated copper arsenate (CCA)-treated wood has been widely used in the Southeastern United States to protect wood products from microbial and fungal decay. The aims of this study were to (1). determine the distribution of arsenic (As), chromium (Cr), and copper (Cu), in soils surrounding CCA-treated wood structures such as decks, fences and poles; and (2). evaluate the impacts of these structures on As, Cr and Cu loading of the soils. Profile and lateral soil samples were collected under CCA-treated decks and adjacent to poles and fences. The results showed elevation of As, Cr and Cu concentrations close to and under the structures, with mean As concentrations as high as 23 mg x kg(-1) close to utility poles compared with less than 3 mg x kg (-1) at distances of about 1.5 m away. Concentrations of As, Cr, and Cu decreased with depth in areas close to CCA-treated poles. However, these results were only apparent in relatively new structures. A combination of weathering and leaching with time may have reduced the impact in older poles. Increased concentrations of As, Cu and Cr were also observed close to CCA-treated decks and fences, with age showing a similar impact. These results are helpful for CCA-treated wood product users to determine the safe use of these structures.

Arsenates↗
PubMed2003

Topical 5-aminolaevulinic acid photodynamic therapy for cutaneous lesions: outcome and comparison of light sources.

BACKGROUND: Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) is increasingly used for superficial non-melanoma skin cancers and their precursors. METHODS: We report our 3-year experience of topical ALA-PDT, with a preliminary comparison of the effects of broadband and laser light sources. RESULTS: We performed 688 treatments on 483 lesions in 207 patients. Complete clearance was achieved in 222/239 lesions of Bowen's disease (BD), superficial basal cell carcinoma (sBCC) and actinic keratosis (AK) (93%) - 117/129 BD (91%), 84/87 sBCC (97%) and 21/23 AK (91%), with a median follow up of 48 weeks. Broadband and laser light sources were of similar efficacy. Recurrences have occurred in 10.3% BD, 4.8% sBCC and 4.8% AK. Adverse effects from PDT were uncommon but included pigmentary change (2%) and minor scarring (2%). How-ever, severe pain was experienced in 16-21% of treatments using the high-output broadband and laser sources, but in only 2% with the low-output xenon arc source. CONCLUSION: Topical ALA-PDT is effective for BD, sBCC and AK and has been an invaluable addition to our dermatology service. Efficacy is similar for broadband and laser light sources, although treatment at higher surface irradiance may be painful, and excellent cosmetic results can be achieved.

Adult↗
PubMed2003

Scalp necrosis in temporal arteritis.

Giant cell arteritis is a systemic disease of the elderly which affects large and medium-sized arteries and which may occur in association with polymyalgia rheumatica. Scalp necrosis is a rare cutaneous complication of giant cell arteritis, and this dermatological presentation is not commonly reported.1-4 Giant cell arteritis should be considered in all elderly patients with scalp ulceration. We describe two patients who presented in this manner.

Aged↗
PubMed2003

Brain metabolism in the cerebellum and visual cortex correlates with neuropsychological testing in patients with Alzheimer's disease.

This study was designed to measure glucose metabolic deficits in areas not typically recognized as abnormal on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans in patients with Alzheimer's disease (AD), and to correlate such findings with subtle neuropsychological impairment. FDG-PET scans on 38 AD patients with no clinical evidence of visual, spatial or motor deficits were acquired on the PET HEAD scanner 40 min following the intravenous administration of 115 microCi.kg-1 of FDG. All FDG-PET scans were analysed blindly using a region of interest (ROI) template with regions for the primary visual cortex (PVC), secondary visual cortex (SVC) and cerebellum. Counts from the ROIs of these regions were normalized to whole brain activity and the results were compared with psychometric and neuropsychological measures. A number of significant correlations were found between these structures and various neuropsychological measures (P<0.05). Specifically, there were significant correlations between clock drawing and the cerebellum activity; memory and activity in the PVC, SVC and cerebellum; social score and activity in the PVC and left cerebellum; judgement and activity in the right SVC and right PVC; and the overall Mini-Mental State Examination and activity in the PVC, SVC and cerebellum. The results of this study suggest that metabolism in areas not typically recognized as abnormal on FDG-PET scans in AD, such as the PVC, SVC and cerebellum, is correlated with deficits in neuropsychological function. This may have important clinical and pathophysiological implications in the study of AD and other illnesses of dementia.

Aged↗
PubMed2002

Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases.

Overexpression of the epidermal growth factor receptor (EGFR) often correlates with an aggressive tumour phenotype and poor prognosis. To examine the relevance of EGFR in colorectal cancer, we determined the expression of EGFR protein in 249 colorectal adenocarcinomas and 42 lymph node metastases using immunohistochemistry. Moreover, we investigated a (CA)(n) dinucleotide repeat polymorphism of the EGFR gene in a subset of 114 tumours. High levels of EGFR protein were observed in 123/249 (49.4%) samples. EGFR expression in colorectal carcinomas correlated with differentiation grade (P=0.014). However, there were no associations with Dukes' stage, site, patient age or gender. EGFR protein expression did not influence survival in this colorectal cancer patient cohort (P>or=0.05). Expression was not identical in paired colorectal tumours and lymph node metastases, with only 17/42 (40.5%) samples showing equivalent EGFR levels (P>0.05). The distribution of the (CA)(n) dinucleotide repeat alleles in colorectal adenocarcinomas was not associated with EGFR protein expression (P>0.05). These results indicate that while EGFR overexpression is a common event in colorectal carcinogenesis, it does not influence patient prognosis.

Adenocarcinoma↗
PubMed2002

Distortion correction and robust tensor estimation for MR diffusion imaging.

This paper presents a new procedure to estimate the diffusion tensor from a sequence of diffusion-weighted images. The first step of this procedure consists of the correction of the distortions usually induced by eddy-current related to the large diffusion-sensitizing gradients. This correction algorithm relies on the maximization of mutual information to estimate the three parameters of a geometric distortion model inferred from the acquisition principle. The second step of the procedure amounts to replacing the standard least squares-based approach by the Geman-McLure M-estimator, in order to reduce outlier-related artefacts. Several experiments prove that the whole procedure highly improves the quality of the final diffusion maps.

Artifacts↗
PubMed2001

Mammalian expression and hollow fiber bioreactor production of recombinant anti-CEA diabody and minibody for clinical applications.

Genetically engineered radiolabeled antibody fragments have shown great promise for the radioimmunoscintigraphy of cancer. Retaining the exquisite specificity of monoclonal antibodies yet smaller in molecular size, antibody fragments display rapid tumor targeting and blood clearance, a more uniform distribution in the tumor, and present a lower potential to elicit an immune response. However, one of the factors that has limited clinical evaluation of these antibody-derived proteins has been the difficulty in expressing and purifying the quantities necessary for clinical trials. This study outlines the capability of mammalian expression for the production of recombinant antibody fragments intended for clinical use. Two anti-carcinoembryonic antigen antibody fragments, the T84.66/212 Flex minibody (scFv-C(H)3) and the T84.66 diabody (scFv dimer) have been previously expressed and have shown excellent radioimaging properties in tumor bearing animals. To proceed toward human studies, these high affinity recombinant fragments and a second minibody version, the T84.66/GS18 Flex minibody, were expressed using a high-level mammalian expression system. Production of all three antibody fragments in a small-scale hollow fiber bioreactor resulted in 137-307 mg of crude antibody harvest. A purification protocol that employed ceramic hydroxyapatite and anion exchange chromatography resulted in 50-150 mg of purified T84.66 diabody and T84.66 minibody. The development of this level of research grade material established conditions for clinical production as well as provided material to complete pre-clinical studies and undertake protein crystallization studies. Scale-up for clinical studies produced 3.4 g of the T84.66 minibody in the harvest. A portion of this material was purified yielding 180 mg of highly purified T84.66 minibody intended for pilot radioimmunoscintigraphy studies of carcinoembryonic antigen (CEA) positive disease.

Antibodies, Monoclonal↗
PubMed2001

Sleep deprivation as a model experimental antidepressant treatment: findings from functional brain imaging.

This paper reviews the functional brain imaging studies in depressed patients treated with sleep deprivation. Sleep deprivation is an excellent experimental model of antidepressant treatments which offer new opportunities to understand the basic neural mechanisms. Its antidepressant effects are efficacious and rapid; sleep deprivation is easy to administer, inexpensive, and relatively safe; it can be studied in patients, normal controls, and animals; and it may lead to new treatments and new paradigms for antidepressant therapies. Seven published papers, coming from five different research centers, using either positron emission tomography (PET) with 18fluorodeoxyglucose (FDG) or single photon emission computerized tomography (SPECT) with Technetium-99-bexamethyl propyleneamine oxime (HMPAO) have relatively consistent findings. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders, and usually the normal controls, in the orbital medial prefrontal cortex, and especially in the ventral portions of the anterior cingulate cortex. Secondly, after sleep deprivation, these hyperactive areas normalize in the responders. The magnitude of the clinical improvement was significantly correlated with decreased local glucose metabolic rate or cerebral blood flow in three studies. The results are consistent with some but not all functional brain imaging studies of antidepressant medications in depressed patients. Finally, a SPECT study using a radioactively labeled D2 receptor antagonist suggests that the antidepressant benefits of sleep deprivation are correlated with endogenous release of dopamine.

Brain↗
PubMed2001

Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Cardiac surgery patients' hematocrits frequently fall to low levels during cardiopulmonary bypass. METHODS: We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category. RESULTS: After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass. CONCLUSIONS: Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.

Aged↗
PubMed2001

Flow mixing and fluid residence times in a model of a ventricular assist device.

To provide a reliable tool for predicting the flow in a clinical sac-type ventricular assist device (VAD), a simplified model VAD was developed prior to this study for the purpose of experimental validation of computer simulations of the time-varying flow on a moving grid. At selected locations in the flow field, flow patterns, vortex core trajectories and velocities were compared between the numerical and physical models during one full pumping cycle. The computer simulations showed qualitatively very good agreement with the experiment. Quantitatively, the agreement was less favourable. In order to investigate flow mixing and to evaluate fluid residence times in the model VAD a new tool has been developed: the numerical simulations were extended by injecting a scalar into the flow domain. These simulations allow investigation of the flow mixing qualitatively by visualisation and quantification of fluid residence times. Experimental assessment of the numerical results using dye injection proved to be favourable. The numerical results have been extended to include some prediction of pressure which have been compared with experimental measurements.

Biomedical Engineering↗
PubMed2001

New sunscreens confer improved protection for photosensitive patients in the blue light region.

BACKGROUND: Some patients with photosensitivity disorders are sensitive to visible radiation. As current commercial sunscreens do not significantly absorb in this region, there is a lack of effective topical photoprotection. To meet this need a new range of sunscreens has been developed incorporating zinc oxide and pigmentary grade titanium dioxide as active ingredients. OBJECTIVES: To determine the effectiveness of the new sunscreens in providing protection for patients with visible radiation photosensitivity. METHODS: In the first part of this study, an in vitro transmission spectrum was obtained. The properties of the new sunscreens, as well as a range of commercial agents, were compared, and a new parameter, photosensitivity protection factor (PPF), was developed. This was used to predict the likely degree of protection the various sunscreens would provide for patients with photosensitivity extending into the visible region. In the second in vivo part of the study, patients with known visible (blue) light photosensitivity were tested using light at 430 +/- 30 nm and the protection factor (PF) at this wavelength was determined. RESULTS: Mean +/- SD PPFs for the new sunscreens were between 5.4 +/- 0.3 and 9.6 +/- 0.3, compared with 4.1 +/- 0.1 for Sun E45 (sun protection factor, SPF 25) and 4.2 +/- 0.1 for RoC Total (SPF 25). The derived in vivo PF for Sun E45 ranged between 1 and 4 (median 2). For the new sunscreens the range was 3 to > 10 (median 8). CONCLUSIONS: This study demonstrates that the new sunscreens do provide protection for patients with sensitivity to visible light (blue light region).

Adult↗
PubMed2001

Conjunctivitis due to Chlamydophila felis (Chlamydia psittaci feline pneumonitis agent) acquired from a cat: case report with molecular characterization of isolates from the patient and cat.

Conjunctivitis due to Chlamydiaceae other than Chlamydia trachomatis is rarely reported because of infrequent occurrence or inadequate investigation. A case of chronic non-trachomatis chlamydial conjunctivitis is described. After full clinical information was supplied to the laboratory, a non-trachomatis chlamydia was recovered from the patient's eye. This organism, and a subsequent isolate from one of the patient's cats, were shown to be indistinguishable examples of the recently described species Chlamydophila felis. The infection was most likely acquired from the patient's cats. A prolonged course of doxycycline was required to eradicate the infection.

AIDS-Related Opportunistic Infections↗
PubMed2001

Variables influencing end-of-life care in children and adolescents with cancer.

BACKGROUND: The purpose of this study was to describe the variables influencing end-of-life care in children and adolescents dying of cancer. MATERIALS AND METHODS: Records of 146 children with cancer who died at Children's Hospital were reviewed for demographics, diagnosis, location of death, withdrawal of life support, use of "do not resuscitate" (DNR) orders, and the length of time that those orders were in effect. RESULTS: Ninety-five patients were evaluated. Fifty-nine died of progressive disease and 36 deaths were therapy-related. Sixty-four percent of disease-related deaths occurred at home with support from home care or hospice. Only 10% of all patients died while receiving maximal aggressive support in the intensive care unit. Age, diagnosis (solid tumor vs. leukemia), cause of death, length of last hospital admission, and the duration of DNR orders had a significant correlation with the place of death and referral to and use of hospice. Thirty-five percent of all patients had hospice support. CONCLUSIONS: Most children who die of cancer die because of progressive disease at home with hospice support. Do not resuscitate orders were written for most patients who died. End-of-life decisions are influenced by patient diagnosis, cause of death, and age.

Adolescent↗
PubMed2001

Characterization of Salmonella associated with pig ear dog treats in Canada.

In the summer of 1999, the incidence of Salmonella enterica serotype Infantis infections in Alberta rose dramatically. Subsequent laboratory and epidemiological investigations established that an outbreak of human disease caused by this organism was occurring across Canada and was associated with pet treats for dogs produced from processed pig ears. Laboratory investigations using phage typing and pulsed-field gel electrophoresis (PFGE) established that isolates of Salmonella serotype Infantis from pig ear pet treats and humans exposed to pig ear pet treats comprised a well-defined subset of all isolates analyzed. Of the 53 subtypes of Salmonella serotype Infantis obtained around the time of the outbreak as defined by PFGE and phage typing, only 6 subtypes were associated with both human infection and isolation from pig ears. Together with information from epidemiological studies, these investigations established pig ear pet treats as the cause of the Salmonella serotype Infantis outbreak. The results are consistent with a model in which contaminated pig ear pet treats constitute a long-term, continuing vehicle for infection of the human population rather than causing temporally delimited point-source outbreaks. During the course of this outbreak, several other Salmonella serotypes were also isolated from pet treats, suggesting these products may be an important source of enteric infection in both humans and dogs. Though isolates of Salmonella serotypes other than Salmonella serotype Infantis from pet treats were also subjected to PFGE and phage typing, no link with human disease could be definitively established, and the contribution of pig ear pet treats to human disease remains unclear. Elimination of bacterial contamination from pet treats is required to reduce the risk of infection from these products.

Alberta↗
PubMed2001

Regional cerebral glucose metabolism in never-medicated patients with schizophrenia.

OBJECTIVE: The purpose of this study was to assess regional cerebral glucose metabolism in patients with schizophrenia who had never received antipsychotic medication and whose olfactory identification ability had been assessed. Two hypotheses were examined. First, the patients were compared with normal controls to determine whether differences in regional cerebral metabolism were apparent. Second, regional rates of metabolism were correlated with olfactory ability and the relation between them determined. METHODS: The patient (n = 26) and control (n = 32) subjects were scanned at rest using positron emission tomography (PET) after administration of 18F-fluorodeoxyglucose (FDG). In addition, the University of Pennsylvania Smell Identification Test was administered to each patient. RESULTS: Patients with schizophrenia had reduced rates of glucose metabolism in the right and left thalamus that reached significance if not corrected for multiple comparisons. However, if a Bonferroni correction was applied over the 27 regions of interest, the differences were not significant. Scores on the Smell Identification Test were negatively correlated with 8 regions of interest. When scores were analyzed using multiple regression, the left frontal cortex and the medial parietal cortex were significant predictors. CONCLUSIONS: The finding of reduced metabolism in the thalami is consistent with some of the previous literature, whereas the negative correlations between specific regions and olfactory function are not consistent with studies using activation paradigms.

Adolescent↗