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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Incidence and predictors of reinfection with Trichomonas vaginalis in HIV-infected women.

BACKGROUND AND OBJECTIVES: The presence of sexually transmitted infections (STIs) may facilitate transmission of HIV to uninfected partners. GOAL: To describe the incidence of reinfection with Trichomonas vaginalis in HIV-infected women and to assess predictors of reinfection. STUDY DESIGN: A retrospective cohort study using data abstracted from medical records of HIV-infected women with at least one diagnosis of trichomoniasis. RESULTS: Approximately one third (36%) of the study population was reinfected with T vaginalis during the follow-up period, with an incidence of 16.4 reinfections per 100 person years. Significant predictors of reinfection included history of another STI (hazard ratio, 1.52; 95% CI, 1.08-2.14) and becoming pregnant during the follow-up period (hazard ratio, 0.59; 95% CI, 0.39-0.87). CONCLUSIONS: There is a high rate of reinfection with T vaginalis in HIV-infected women. Further research that includes information on sexual partners should be conducted to better describe the reinfection patterns of trichomoniasis.

Adult↗
PubMed1999

Critical flanking sequences of PU.1 binding sites in myeloid-specific promoters.

The myeloid-specific transcription factor PU.1 is essential for expression of p47(phox), a component of the superoxide-forming phagocyte NADPH oxidase. The consensus PU.1 binding sequence (GAGGAA) is located on the non-coding strand from position -40 to -45 relative to the transcriptional start site of the p47phox promoter. A promoter construct extending to -46 was sufficient to drive tissue-specific expression of the luciferase reporter gene, but extension of the promoter from -46 to -48 resulted in a significant increase in reporter expression. Mutations of the nucleotides G at -46 and/or T at -47 reduced both reporter expression and PU.1 binding, whereas mutations at -48 had no effect. The PU.1 binding avidity of these sequences correlated closely with their capacity to dictate reporter gene transcription. In parallel studies on the functional PU.1 site in the promoter of CD18, mutations of nucleotides G and T at positions -76 and -77 (corresponding to -46 and -47, respectively, of the p47phox promoter) reduced PU.1 binding and nearly abolished the contribution of this element to promoter activity. We conclude that the immediate flanking nucleotides of the PU.1 consensus motif have significant effects on PU.1 binding avidity and activity and that this region is the dominant cis element regulating p47phox expression.

Base Sequence↗
PubMed1999

Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.

Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Predictive markers of HIV-related weight loss and determination of differences between populations with weight loss stratified by opportunistic processes.

OBJECTIVE: To describe factors predictive of >10% weight loss among enrolled participants in clinical trials of the AIDS Clinical Trial Group (ACTG). DESIGN: A retrospective analysis of data from selected ACTG antiretroviral clinical trials completed prior to 1996 (ACTG 116, 117, 155, 175, and 241), which did not include protease inhibitors. METHODS: Data were analyzed in Cox proportional hazards models to determine significant predictors for >10% weight loss while on study. Weight loss occurring within 30 days before or after an opportunistic infection (OI) was defined as "OI-associated." Both univariate and multivariate models were considered; gender-specific models were also analyzed to provide insight into potential gender differences in predictors of weight loss. RESULTS: We found that substantial weight loss is a frequent occurrence among those enrolled in clinical trials of antiretroviral agents; approximately 15% of subjects in the studies considered experienced >10% weight loss. CD4 cell count and HIV-1 RNA at week 8, Karnofsky score, and injection drug use status were significant multivariate predictive markers for weight loss associated with an OI; baseline weight, hemoglobin, triglycerides, and gender were additional predictors for weight loss not associated with an OI. CONCLUSIONS: This is the first study to characterize the association between baseline viral load and future weight loss. Baseline and week 8 immunologic parameters as well as measures of baseline symptomatology were significant predictors of weight loss associated and not associated with an OI.

AIDS-Related Opportunistic Infections↗
PubMed1999

Advising parents of asthmatic children on passive smoking: randomised controlled trial.

OBJECTIVE: To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke. DESIGN: Randomised controlled trial. SETTING: Tayside and Fife, Scotland. PARTICIPANTS: 501 families with an asthmatic child aged 2-12 years living with a parent who smoked. INTERVENTION: Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child's health. MAIN OUTCOME MEASURES: Salivary cotinine concentrations in children, and changes in reported smoking habits of the parents 1 year after the intervention. RESULTS: At the second visit, about 1 year after the baseline visit, a small decrease in salivary cotinine concentrations was found in both groups of children: the mean decrease in the intervention group (0.70 ng/ml) was slightly smaller than that of the control group (0.88 ng/ml), but the net difference of 0.19 ng/ml had a wide 95% confidence interval (-0.86 to 0.48). Overall, 98% of parents in both groups still smoked at follow up. However, there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking. CONCLUSIONS: A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children's exposure to environmental tobacco smoke. The intervention may have made some parents less inclined to stop smoking. If a clinician believes that a child's health is being affected by parental smoking, the parent's smoking needs to be addressed as a separate issue from the child's health.

Adult↗
PubMed1999

An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis.

OBJECTIVE: To critically review the body of clinical trials that refute or support the efficacy of antihistamines in relieving pruritus in patients with atopic dermatitis. DESIGN: Review of MEDLINE from 1966 through March 1999, the Cochrane Database of Systematic Reviews, and Best Evidence to identify therapeutic trials of antihistamines in patients with atopic dermatitis. MAIN OUTCOME MEASURES: All randomized controlled trials or clinical trials of antihistamines used in the treatment of atopic dermatitis. We found 16 studies throughout the literature. RESULTS: Large, randomized, double-blind, placebo-controlled clinical trials with definitive conclusions (grade A trials) have not been performed. Two grade B trials (small, rigorous, randomized trials with uncertain results due to moderate to high alpha or beta error) refuted the use of antihistamines in relieving pruritus. One grade B trial supported the efficacy of antihistamines in relieving pruritus. All remaining trials (grade C) lacked placebo controls or randomization, or contained fewer than 20 patients in each treatment group. CONCLUSIONS: Although antihistamines are often used in the treatment of atopic dermatitis, little objective evidence exists to demonstrate relief of pruritus. The majority of trials are flawed in terms of the sample size or study design. Based on the literature alone, the efficacy of antihistamines remains to be adequately investigated. Anecdotally, sedating antihistamines have sometimes been useful by virtue of their soporific effect and bedtime use may be warranted. There is no evidence to support the effectiveness of expensive nonsedating agents.

Clinical Trials as Topic↗
PubMed1999

Posterior fixation sutures: a revised mechanical explanation for the fadenoperation based on rectus extraocular muscle pulleys.

PURPOSE: To determine the effect of the rectus extraocular muscle pulleys on the fadenoperation, an operation designed to fixate the posterior muscle belly to the underlying retroequatorial sclera. METHODS: First, duction into the field of action of the operated-on muscle was quantified retrospectively after fadenoperation. Magnetic resonance imaging was then performed prospectively after surgery to verify anatomic changes. Forced duction testing was performed prospectively during surgery before and after faden placement. Finally, computed tomography in a cadaver containing radiographic markers was performed prospectively to determine the effect of fadenoperation on the position of the medial rectus insertion relative to its pulley. RESULTS: Mean maximum adduction after medial rectus fadenoperation was 18 degrees (range, 10 to 25 degrees; 13 eyes). Fadenoperations combined with large medial rectus recessions restricted adduction more than fadenoperations combined with smaller recessions (P = .019), but even fadenoperations without recessions substantially restricted adduction. Mean maximum abduction after lateral rectus fadenoperation was 40 degrees (range, 25 to 45 degrees; four eyes). Axial magnetic resonance imaging in two eyes demonstrated a smaller loss of muscle tangency to the globe during contraction than predicted by geometric models. Forced ductions in nine patients performed immediately after faden placement demonstrated a new mechanical restriction to duction toward the operated-on muscle. Cadaveric computed tomographic scans demonstrated posterior displacement of the medial rectus pulley during adduction after fadenoperation. CONCLUSIONS: Posterior fixation sutures do not significantly decrease muscle torque during contraction. Because posterior fixation sutures posteriorly displace the pulley sleeve during duction toward the operated-on muscle, the mechanical restriction after surgery probably represents the force deforming the pulley. This mechanical restriction may account for the limitation in duction seen after fadenoperation.

Eye Movements↗
PubMed1999

Digital mammography: comparison of adaptive and nonadaptive CAD methods for mass detection.

RATIONALE AND OBJECTIVES: The authors compared the performance of adaptive and nonadaptive computer-aided diagnostic (CAD) methods for breast mass detection with digital mammography. MATERIALS AND METHODS: Both adaptive and nonadaptive modular CAD methods employed recent advances in multiresolution and mutiorientation wavelet transforms for improved feature extraction. The nonadaptive method uses fixed parameters for the image preprocessing modules. The adaptive method, a new class of algorithms, adapts to image content by selecting parameters for the image preprocessing modules within a parameter range. Comparison of the two methods was performed for each individual CAD module with a region-of-interest (ROI) database containing all mass types and normal tissue. RESULTS: Receiver operating characteristic (ROC) analysis clearly demonstrated an improvement in performance for the three adaptive modules and a significant overall difference between the two methods. The average ROC area index (Az) values were 0.86 and 0.95 for the nonadaptive and adaptive methods, respectively. The corresponding P value is .0145. For a previously reported database of full mammographic images containing 50 abnormal cases with all mass types and 50 normal images, the adaptive CAD method had a sensitivity of 96% (1.71 false-positive results per image) compared with 89% (1.91 false-positive results per image) for the nonadaptive CAD method. CONCLUSION: The adaptive CAD method demonstrated better performance. A study is in progress to determine the generalizability of the adaptive CAD method by applying it to larger retrospective image databases with different film digitizers.

Algorithms↗
PubMed1999

Magnetic resonance imaging after surgical transposition defines the anteroposterior location of the rectus muscle pulleys.

INTRODUCTION: Connective tissue pulleys serve as the functional origins of the rectus extraocular muscles (EOMs) and constrain the sideslip of the posterior EOM bellies after transposition surgery. Anterior to the pulleys, EOM paths appreciably displace to reach their transposed insertions. The inflection points in the EOM paths from minimal posterior displacement to maximal anterior displacement should define the anteroposterior location of the EOM pulleys after transposition. METHODS: Contiguous cross-sectional magnetic resonance images were obtained in planes perpendicular to the long axis of the orbit over its entire anteroposterior extent before and after operation in 6 patients who underwent rectus muscle transposition surgery. Four patients underwent full tendon width transposition of the vertical rectus muscles laterally for lateral rectus palsy. Two of these patients had augmentation of the transposition with sutures that fixated the temporal margins of the transposed muscles posteriorly to the sclera adjacent to the borders of the lateral rectus muscle. One patient underwent full tendon width transposition of the horizontal rectus muscles superiorly for superior rectus palsy. One patient underwent full tendon width transposition of both lateral rectus muscles inferiorly for "A" pattern esotropia. Paths of EOMs were defined relative to the area centroid of the orbit. Pulley locations were inferred from EOM paths. The postoperative change in EOM pulley location was obtained by subtracting the preoperative pulley location from the postoperative pulley location for each image plane. RESULTS: For all patients, the postoperative change in EOM belly location was relatively small posterior to the globe-optic nerve junction. The 2 patients with abducens palsy who underwent placement of posterior augmentation sutures, however, demonstrated a significantly larger displacement of the posterior vertical rectus paths compared with similar patients who did not receive augmentation sutures. For all horizontally transposed vertical rectus muscles and inferiorly transposed lateral rectus muscles, the inflection of the EOM path began 3 mm anterior to the globe-optic nerve junction. For the superiorly transposed medial rectus muscle and lateral rectus muscle, the inflection began 6 mm anterior to the globe-optic nerve junction. CONCLUSIONS: The anteroposterior locations of the EOM pulleys can be defined by analysis of EOM displacement after transposition surgery. Augmentation of transpositions by posterior suturing displaces the EOM pulleys substantially more than nonaugmented transpositions.

Abducens Nerve↗
PubMed1999

Instrument-induced measurement errors during strabismus surgery.

PURPOSE: The purpose of this study was to determine the clinical setting where errors in measurements of muscle position during strabismus surgery made by the Scott curved ruler or by calipers become important and to characterize the magnitude of those errors. METHODS: Geometric analysis was used to determine the measurement error between true arc lengths of 3.0 to 20.0 mm versus Scott curved ruler measurements and caliper measurements for axial lengths ranging from 18 to 30 mm. RESULTS: For measurements less than 9.0 mm, neither the Scott curved ruler nor calipers had any clinically important measurement error for any axial length. For axial lengths substantially smaller than 21 mm or larger than 24 mm, the Scott curved ruler, although more accurate than calipers, caused clinically important measurement errors with arc length measurements as small as 12 mm in very small eyes and 14 mm in large eyes. For axial lengths of 30 mm or more, both calipers and the Scott curved ruler had similar accuracy for measuring long arc lengths. CONCLUSIONS: Both the Scott curved ruler and calipers are accurate in measuring arc lengths 9.0 mm or less. For longer arc length measurements, accuracy becomes dependent on axial length. The Scott curved ruler, although substantially more accurate than calipers for most common axial lengths, can introduce clinically important measurement errors when measuring arc lengths as small as 12 mm. Axial length should be considered when measuring muscle position during strabismus surgery.

Anthropometry↗
PubMed1999

Characterisation of tissue-specific oligosaccharides from rat brain and kidney membrane preparations enriched in Na+,K+-ATPase.

The organ-specific nature of the glycosylation of Na+,K+-ATPase-enriched preparations from kidney and brain tissues has earlier been indicated by the use of lectin-staining techniques. Na+,K+-ATPase is ubiquitous and abundant, and subject to upregulation during cell-division and in certain pathological conditions. Lectins specific for the different carbohydrates displayed by the Na+,K+-ATPases may, therefore, be useful carriers/mediators in tissue-specific targeting. N-linked oligosaccharides purified from Na+,K+-ATPase-enriched preparations from rat brain and kidney were consequently characterised in detail in this study using weak anion exchange and normal phase HPLC (combined with serial glycosidase digestions) and matrix-assisted laser desorption/ionisation mass spectrometry. The oligomannose series of glycans were most abundant in the brain tissue preparation and this contrasted with the renal-associated oligosaccharides that were dominated by families of tetra-antennary glycans (with/without a core fucose) with up to four lactosaminylglycan residues in either branched or linear formation.

Animals↗
PubMed1999

Fibrin microbeads (FMB) as biodegradable carriers for culturing cells and for accelerating wound healing.

We have developed biodegradable fibrin-derived microbeads as potent cell carriers. The fibrin-derived microbeads, 50-200 microm in diameter, were tested for their attachment to a wide range of cell types. Fibrin-derived microbeads were shown to be greatly haptotactic to cells (such as endothelial cells, smooth muscle cells and fibroblasts), which respond to fibrinogen in contrast to keratinocytes and different cell lines derived from leukocytic lineage. The cells on fibrin-derived microbeads could be maintained for more than 10 d and achieved a high density. 31P-nuclear magnetic resonance was employed to monitor phosphate metabolism in cells, with densities on the order of 100 million cells per g of fibrin-derived microbeads. The 31P-nuclear magnetic resonance adenosine triphosphate and phosphocreatine signals, equivalent to the signal obtained with perfused normal skin, indicated that metabolism of cells on fibrin-derived microbeads was responsive to oxygenation and nutrients. Light, fluorescent, and confocal laser microscopy revealed that the porous fibrin-derived microbeads accommodate up to 200-300 cells due to their high surface area which minimized contact inhibition. Cells could degrade the fibrin-derived microbeads and be transferred to seed culture flasks without trypsinization. In a pig skin wound healing model, fibrin-derived microbeads + fibroblasts were transplanted into full thickness punch wounds. This procedure was compared with other treatment modalities, such as the addition of human platelet-derived growth factor BB or fibrin-derived microbeads alone. By the third day after wounding, only the wounds in which fibroblasts on fibrin-derived microbeads were added showed significant formation of granulation tissue. Based on the above, we project many uses of our novel fibrin-derived microbead technology for cell culturing, wound healing and tissue engineering.

Animals↗