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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 37 records · Page 2Linked to original sources

Timing of postoperative adjustment in adjustable suture strabismus surgery.

PURPOSE: The use of adjustable sutures in strabismus surgery has increased the rate of surgical success. Little data are available on the optimum timing for postoperative adjustment after strabismus surgery. We wanted to compare 2 common practices of adjustable suture technique after strabismus surgery. METHODS: Two comparable groups of 40 patients each, who had strabismus surgery with adjustable suture technique, were prospectively studied. Group A had early adjustment the same day of the surgery about 6 hours after the operation, and group B had late adjustment the next day about 24 hours after the operation. Subjective scoring tables were used to evaluate the pain felt by the patient before, during, and after the adjustment and any difficulties of the adjustment process. Requirements of postoperative pain medications and final alignment 6 weeks after surgery were also compared. RESULTS: Despite adequate statistical power, no significant differences were found between the groups regarding pain before, during, and after adjustment, difficulties performing the adjustment, and final alignment after 6 weeks (P > .05). Both adjustment schedules were equally associated with mild to moderate pain before, during, and after the adjustment. In the first 24 hours after surgery, no overall difference in the use of pain medications was found. Nausea and vomiting in the first 24 postoperative hours were more common in the early adjustment group (P = .02). CONCLUSION: The surgeon can feel free to choose the timing for postoperative adjustment. However, when performing an early adjustment, the surgeon should be especially prepared to control nausea and vomiting.

Adult↗

Fibrin and wound healing.

Although hemostasis is the major role of fibrin in wound repair, once the clot is present the wound cells must deal with it. The invasion and clearing of fibrin by these cells involves multiple complex processes that may go array XXX and delay wound repair. A good example, of the latter is leg ulcers. These chronic wounds contain a plethora of proteases that digest fibronectin and growth factors in the fibrin clot resulting in a corrupt provisional matrix that no longer supports reepithelialization or granulation tissue formation. Every good wound care provider knows that these wounds will not heal unless the corrupt matrix is removed by vigorous debridement that stimulates the accumulation of a competent provisional matrix.

Epithelial Cells↗

False-positive reduction in CAD mass detection using a competitive classification strategy.

High false-positive (FP) rate remains to be one of the major problems to be solved in CAD study because too many false-positively cued signals will potentially degrade the performance of detecting true-positive regions and increase the call-back rate in CAD environment. In this paper, we proposed a novel classification method for FP reduction, where the conventional "hard" decision classifier is cascaded with a "soft" decision classification with the objective to reduce false-positives in the cases with multiple FPs retained after the "hard" decision classification. The "soft" classification takes a competitive classification strategy in which only the "best" ones are selected from the pre-classified suspicious regions as the true mass in each case. A neural network structure is designed to implement the proposed competitive classification. Comparative studies of FP reduction on a database of 79 images by a "hard" decision classification and a combined "hard"-"soft" classification method demonstrated the efficiency of the proposed classification strategy. For example, for the high FP sub-database which has only 31.7% of total images but accounts for 63.5% of whole FPs generated in single "hard" classification, the FPs can be reduced for 56% (from 8.36 to 3.72 per image) by using the proposed method at the cost of 1% TP loss (from 69% to 68%) in whole database, while it can only be reduced for 27% (from 8.36 to 6.08 per image) by simply increasing the threshold of "hard" classifier with a cost of TP loss as high as 14% (from 69% to 55%). On the average in whole database, the FP reduction by hybrid "hard"-"soft" classification is 1.58 per image as compared to 1.11 by "hard" classification at the TP costs described above. Because the cases with high dense tissue are of higher risk of cancer incidence and false-negative detection in mammogram screening, and usually generate more FPs in CAD detection, the method proposed in this paper will be very helpful in improving the performance of early detection of breast cancer with CAD.

Biophysical Phenomena↗

Does passive smoking increase the frequency of health service contacts in children with asthma?

BACKGROUND: Passive smoking is a major cause of respiratory morbidity in children. However, few studies give accurate estimates of the health effects of passive smoking in children with asthma using an objective measure of exposure. The effects of passive smoking using salivary cotinine levels to measure exposure were investigated. METHODS: A sample of 438 children aged 2-12 years with asthma who had a parent who smoked were recruited in Tayside and Fife, Scotland. Health service contacts for asthma, assessed from GP case records, were used as a proxy for morbidity. RESULTS: A weak U-shaped relationship was found between the salivary cotinine level and health service contacts for asthma: compared with low cotinine levels those with moderate cotinine levels had a reduced contact rate (relative rate (RR) = 0.91, 95% confidence interval (CI) 0.80 to 1.05), whereas high cotinine levels were associated with an increased rate of contact (RR = 1.19, 95% CI 1.05 to 1.37). In contrast, a strong association was seen with the amount the parent reported smoking in front of the child: the higher the level the fewer visits were made for asthma (RR for everyday exposure = 0.66, 95% CI 0.56 to 0.77). This effect was not seen for non-respiratory visits. Demographic factors, age of child, and number of children in the family all had a powerful effect on the number of visits for asthma. The parents' perception of asthma severity was associated with visit frequency independent of actual severity (derived from drug treatment). CONCLUSION: High levels of parental smoking in the home are associated with a reduction in health care contacts for asthma. This could be due to a lack of awareness of asthma symptoms among heavy smokers or a reluctance to visit the GP. Children with asthma who have parents who smoke heavily may not be receiving adequate management.

Asthma↗

Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphosphate-induced Ca2+ store depletion.

Calreticulin (CRT) is a highly conserved Ca(2+)-binding protein that resides in the lumen of the endoplasmic reticulum (ER). We overexpressed CRT in Xenopus oocytes to determine how it could modulate inositol 1,4,5-trisphosphate (InsP(3))-induced Ca(2+) influx. Under conditions where it did not affect the spatially complex elevations in free cytosolic Ca(2+) concentration ([Ca(2+)](i)) due to InsP(3)-induced Ca(2+) release, overexpressed CRT decreased by 46% the Ca(2+)-gated Cl(-) current due to Ca(2+) influx. Deletion mutants revealed that CRT requires its high capacity Ca(2+)-binding domain to reduce the elevations of [Ca(2+)](i) due to Ca(2+) influx. This functional domain was also required for CRT to attenuate the InsP(3)-induced decline in the free Ca(2+) concentration within the ER lumen ([Ca(2+)](ER)), as monitored with a "chameleon" indicator. Our data suggest that by buffering [Ca(2+)](ER) near resting levels, CRT may prevent InsP(3) from depleting the intracellular stores sufficiently to activate Ca(2+) influx.

Animals↗

Melanoma lymphoscintigraphy and lymphatic mapping.

Lymphoscintigraphy in melanoma has proven to be a reliable method to identify regional lymph nodes at risk for metastases. The first lymph node to drain a cutaneous lesion, the sentinel lymph node (SLN), is predictive of the metastatic status of the regional lymph node group. Lymphatic mapping allows for the identification of the SLN and for selective lymph node sampling. Selective lymph node sampling is less invasive and because only a small quantity of high-risk tissue is submitted for pathological examination, it allows for a more complete and comprehensive pathological examination, which identifies melanoma with up to 100 times the sensitivity of conventional examinations.

Humans↗

Role of redox-regulated transcription factors in inflammation, aging and age-related diseases.

A progressive rise of oxidative stress due to the altered redox homeostasis appears to be one of the hallmarks of the aging process. Reactive oxygen species (ROS) also serve as signaling agents for inflammation, a systemic defensive reaction against microbial pathogens and other foreign bodies. Changes in the pattern of gene expression through ROS-sensitive transcription factors give rise to both aging and inflammation phenotypes. Chronic oxidative stress and inflammatory reaction also lead to many age-associated diseases such as atherosclerosis and arthritis. Transcription factors that are directly influenced by ROS and proinflammatory cytokines include nuclear factor kappa B (NF-kappaB), activator protein 1 (AP-1), specificity protein 1 (Sp1), peroxisome proliferator-activated receptors (PPARs) and other members of the nuclear receptor superfamily. Here we describe the basic components of the intracellular redox control machinery and their dysregulation with age leading to altered transcription factor function and age-associated pathophysiology.

Aging↗

Angiogenesis in wound healing.

During wound healing, angiogenic capillary sprouts invade the fibrin/fibronectin-rich wound clot and within a few days organize into a microvascular network throughout the granulation tissue. As collagen accumulates in the granulation tissue to produce scar, the density of blood vessels diminishes. A dynamic interaction occurs among endothelial cells, angiogenic cytokines, such as FGF, VEGF, TGF-beta, angiopoietin, and mast cell tryptase, and the extracellular matrix (ECM) environment. Specific endothelial cell ECM receptors are critical for these morphogenetic changes in blood vessels during wound repair. In particular, alpha(v)beta3, the integrin receptor for fibrin and fibronectin, appears to be required for wound angiogenesis: alpha(v)beta3 is expressed on the tips of angiogenic capillary sprouts invading the wound clot, and functional inhibitors of alpha(v)beta3 transiently inhibit granulation tissue formation. Recent investigations have shown that the wound ECM can regulate angiogenesis in part by modulating integrin receptor expression. mRNA levels of alpha(v)beta3 in human dermal microvascular endothelial cells either plated on fibronectin or overlaid by fibrin gel were higher than in cells plated on collagen or overlaid by collagen gel. Wound angiogenesis also appears to be regulated by endothelial cell interaction with the specific three-dimensional ECM environment in the wound space. In an in vitro model of human sprout angiogenesis, three-dimensional fibrin gel, simulating early wound clot, but not collagen gel, simulating late granulation tissue, supported capillary sprout formation. Understanding the molecular mechanisms that regulate wound angiogenesis, particularly how ECM modulates ECM receptor and angiogenic factor requirements, may provide new approaches for treating chronic wounds.

Animals↗

Adult-onset recalcitrant eczema: a marker of noncutaneous lymphoma or leukemia.

BACKGROUND: Generalized eczema or erythroderma may be the presenting sign of cutaneous T-cell lymphoma. Additionally, intractable pruritus has been associated with Hodgkin's lymphoma. However, reports of adult-onset eczematous dermatitis has rarely been linked to noncutaneous lymphoproliferative disorders. OBSERVATIONS: We observed one patient in 1993 who had the onset of intractable dermatitis characterized by prurigo nodularis-like lesions and widespread erythematous plaques. After 18 months of cutaneous symptoms he experienced dyspnea. At this time Hodgkin's disease was diagnosed. This observation prompted us to evaluate subsequent patients with adult-onset eczema who were poorly responsive to therapy and in whom an obvious cause could not be determined. Over the next 24 months we identified an additional 2 patients with lymphoma who met this criteria. CONCLUSION: Unexplained eczema of adult onset may be associated with an underlying lymphoproliferative malignancy. When a readily identifiable cause (eg, contactants, drugs, or atopy) is not found, a systematic evaluation should be pursued. Patients should be evaluated with a careful physical examination, complete blood cell counts, peripheral blood smears, chest roentgenography, computed tomography of the chest and abdomen, and serum protein electrophoresis.

Adult↗

Facial asymmetry in superior oblique muscle palsy and pulley heterotopy.

INTRODUCTION: Some observers have considered facial asymmetry as characteristic of congenital superior oblique muscle (SO) palsy. However, recent orbital imaging studies have determined that incomitant vertical strabismus resembling SO palsy can be caused by heterotopic rectus muscle pulleys. This finding suggests that facial asymmetry may predict the presence of abnormal orbital anatomy rather than be secondary to ocular torticollis. METHODS: Subjects who underwent orbital computed tomography or magnetic resonance imaging were divided into 5 groups based on clinical evaluation and previously established imaging criteria: (1) congenital SO palsy; (2) acquired SO palsy; (3) strabismus with pulley heterotopy; (4) strabismus without SO palsy or pulley heterotopy; and (5) orthotropic subjects. Frontal photographs were digitized and the following 3 facial morphometric features recorded: (1) angle of inclination of each orbit; (2) relative facial size; and (3) facial angle. RESULTS: The 79 subjects who underwent imaging were divided into the 5 groups as follows: 6 with congenital SO palsy; 7 with acquired SO palsy; 20 with pulley heterotopy; 26 with strabismus without SO palsy or pulley heterotopy; and 20 control subjects. All subjects with either congenital or acquired SO palsy had torticollis. Multivariate analysis demonstrated no significant differences in any of the 3 facial morphometric features among any of the groups. CONCLUSION: Facial asymmetry as assessed by these 3 morphometric features is not useful in distinguishing between congenital SO palsy or pulley heterotopy and other acquired forms of strabismus. This finding casts doubt on the relationship between ocular torticollis and facial asymmetry.

Adolescent↗

Positron emission tomography in initial staging and diagnosis of persistent or recurrent disease.

Positron emission tomography (PET) constitutes a major advance in the diagnosis, staging, prognostic assessment, and follow-up of lung cancer. However, it is not a magic bullet that can solve all of the uncertainties that beguile the imaging of this disease. Small lesions, particularly those in the brain, may often be missed with PET, and three-dimensional localization of suspected sites may also be unreliable. We are still learning how best to apply this new technology in an environment that demands the efficient use of medical resources. PET will probably be used most enthusiastically in the prethoracotomy staging of patients who are considered operable or probably operable on the basis of computed tomography and in the assessment of treatment response and disease recurrence when clinical management will be determined by prompt recognition of these events.

Brain Neoplasms↗