Colonoscopy vs CT colonography to screen for colorectal neoplasia in average-risk patients.
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Colonic Polyps↗
Biomedical subjects
M E Baker
Publications and source records attributed to M E Baker.
Computer-aided detection (CAD) for CT colonography: a tool to address a growing need.
Colorectal cancer is the third most common cancer in both men and women. It is estimated that in 2004, nearly 147,000 cases of colon and rectal cancer will be diagnosed in the USA, and approximately 57,000 people would die from the disease; however, only 44% of the eligible population undergoes any type of colorectal cancer screening. Many reasons have been identified for non-compliance, with key ones being patient comfort, bowel preparation and cost. Virtual colonoscopy derived from computed tomography (CT) images is gaining broader acceptance as a screening method for colorectal neoplasia. Our research suggests that computer-aided detection (CAD) as a second reader has great potential in improving polyp detection. The ColonCAD prototype presented in this paper was developed and tested on cases representative of the variability and quality in true clinical practice. Results of this study with 150 patients demonstrate that: the developed algorithm generalises well: the sensitivity for polyps > or = 6 mm is on average 90%; and the median false positive rate is a manageable 3 per volume.
Algorithms↗
Timed barium oesophagram: better predictor of long term success after pneumatic dilation in achalasia than symptom assessment.
BACKGROUND: Symptom relief post pneumatic dilation is traditionally used to assess treatment success in achalasia patients. Recently, we showed that symptom relief and objective oesophageal emptying are concordant in about 70% of patients, while up to 30% of achalasia patients report near complete symptom relief despite poor oesophageal emptying of barium. AIMS: We now report the results of long term clinical follow up in these two groups of achalasia patients, assessing differences in symptomatic remission rates. METHODS: Achalasia patients undergoing pneumatic dilation since 1995 were evaluated both symptomatically and objectively at regular intervals. Pre and post dilation symptoms were recorded. Barium column height was measured five minutes after ingesting a fixed volume of barium per patient to assess oesophageal emptying. Patients who initially reported near complete symptom relief were divided into two groups based on objective findings on barium study: (1) complete oesophageal emptying (concordant group), and (2) poor oesophageal emptying (discordant group). Patients were followed prospectively for symptom recurrence. RESULTS: Thirty four patients with complete symptom relief post pneumatic dilation were identified. In 22/34 (65%) patients, the degree of symptom and barium height improvements was similar (concordant group). In 10/34 (30%) patients, there was < 50% improvement in barium height (discordant group). Significantly (p<0.001) more discordant (9/10; 90%) than concordant (2/22; 9%) patients failed therapy at the one year follow up. Seventeen of 22 (77%) concordant patients were still in remission while all discordant patients had failed therapy by six years of follow up. Length of time in symptom remission (mean (SEM)) post pneumatic dilation was significantly (p=0.001) less for the discordant group (18.0 (3.6) months) compared with the concordant group (59.0 (4.8) months). CONCLUSIONS: (1) Poor oesophageal emptying is present in nearly 30% of achalasia patients reporting complete symptom relief post pneumatic dilation. (2) The majority (90%) of these patients will fail within one year of treatment. (3) Timed barium oesophagram is an important tool in the objective evaluation of achalasia patients post pneumatic dilation.
Adult↗
Recent insights into the origins of adrenal and sex steroid receptors.
The recent cloning by Thornton (2001) of estrogen, progesterone and corticoid receptors from lamprey provides important insights into the early evolution of adrenal and sex steroid receptors and an opportunity to elucidate the ancient steroids that regulated gene transcription. Inclusion of lamprey sequences in a steroid receptor phylogeny indicates that the estrogen receptor is the most ancient of these receptors, followed by the progesterone receptor and the corticoid receptor. Thornton proposed that estradiol was the earliest of the steroids to activate a steroid receptor. An alternative hypothesis is that a steroid in the Delta(5) pathway activated the ancestral estrogen receptor.
Adrenal Cortex Hormones↗
Albumin, steroid hormones and the origin of vertebrates.
Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and various phytochemicals and xenobiotics that bind to receptors for steroids and other lipophilic hormones. Despite albumin's low affinity (K(d) approximately 10(-4) M to 10(-6) M) for these lipophilic compounds, the high concentration of albumin in serum makes this protein a major carrier of steroids and lipophilic hormones and a regulator of their access to receptors. Albumin also functions as a sink for xenobiotics, diminishing the binding of xenobiotics to hormone receptors and other cellular proteins. This protects animals from endocrine disruption by xenobiotics. We propose that these properties of albumin were important in protochordates and primitive vertebrates, such as jawless fish, about 600 to 530 million years ago, just before and during the Cambrian period. It is at that time that the ancestral receptors of adrenal and sex steroids - androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins - arose in multicellular animals. Albumin regulated access of steroids to their receptors, as well as protecting animals from endocrine disruptors, such as phytochemicals, fungal chemicals and phenolics, and other chemicals formed at hydrothermal vents by geochemical processes. Thus, animals in which albumin expression was high had a selective advantage in regulating the steroid response and avoiding endocrine disruption by xenobiotics.
Adrenal Cortex Hormones↗
Deletion of 12 carboxyl-terminal residues from pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase affects steroid metabolism.
Pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase (3alpha/beta,20beta-HSD) is 80-85% identical to human, rat, and mouse carbonyl reductases. However, pig 3alpha/beta,20beta-HSD contains an extra 12 amino acids at its COOH-terminus that these other mammalian carbonyl reductases lack. We constructed a pig 3alpha/beta,20beta-HSD mutant, G278opal, which lacks these amino acids and found that compared to wild-type 3alpha/beta,20beta-HSD, G278opal has a 10-fold lower catalytic efficiency for testosterone and progesterone. G278opal also has lower 3alpha- and 20beta-reductase and increased 3beta-reductase activity compared to wild-type 3alpha/beta,20beta-HSD. Binding of NADPH to G278opal was similar to that of wild-type 3alpha/beta,20beta-HSD. The recently determined three-dimensional structure of 3alpha/beta,20beta-HSD, without a steroid substrate, shows the 12 COOH-terminal amino acids in a random configuration. Our data indicate that the 12 COOH-terminal amino acids have a role in steroid metabolism suggesting that binding of steroid to wild-type 3alpha/beta,20beta-HSD induces a conformational change in which the 12 COOH-terminal amino acids interact with the steroid substrate.
20-Hydroxysteroid Dehydrogenases↗
Hydroxysteroid dehydrogenases: ancient and modern regulators of adrenal and sex steroid action.
The adrenal and sex steroids receptor clade arose from an ancestral nuclear receptor in a primitive vertebrate at least 540 million years ago during the early Cambrian. At that time, these receptors had less specificity for their canonical ligands than their descendents in mammals have, which raises the question of how specificity for responses to different steroids was regulated. We propose that hydroxysteroid dehydrogenases that metabolized functional groups at different sites on steroids (e.g. C3, C11, C17 and C20) had a key role in providing specificity for steroid regulation of gene transcription in primitive vertebrates. Later, with increased physiological complexity in land animals due to innovations such as the placenta, hydroxysteroid dehydrogenases were recruited for new roles in regulating steroid-mediated physiological responses. Hydroxysteroid dehydrogenases in fish, amphibia and mammals are likely have different affinities for some xenobiotics, which needs to be considered in evaluating their hazards as endocrine disruptors.
Adrenal Cortex Hormones↗
Evolution of 17beta-hydroxysteroid dehydrogenases and their role in androgen, estrogen and retinoid action.
17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) regulate androgen and estrogen concentrations in mammals. By 1995, four distinct enzymes with 17beta-HSD activity had been identified--17beta-HSD-types 1 and 3, which, in vivo, are NADPH-dependent reductases; and 17beta-HSD-types 2 and 4, which, in vivo, are NAD(+)-dependent oxidases. Since then, six additional enzymes with 17beta-HSD activity have been isolated from mammals. With the exception of 17beta-HSD-type 5, which belongs to the aldoketo-reductase (AKR) family, these 17beta-HSDs belong to the short chain dehydrogenase/reductase (SDR) family. Several 17beta-HSDs appear to be examples of convergent evolution. That is, 17beta-HSD activity arose several times from different ancestors. Some 17beta-HSDs share a common ancestor with retinoid oxido-reductases and have retinol dehydrogenase activity. 17beta-HSD-types 2, 6 and 9 appear to have diverged from ancestral retinoid dehydrogenases early in the evolution of deuterostomes during the Cambrian, about 540 million years ago. This coincided with the origin of nuclear receptors for androgens and estrogens suggesting that expression of 17beta-HSDs had an important role in the early evolution of the physiological response to androgens and estrogens.
11-beta-Hydroxysteroid Dehydrogenases↗
Radiologic evaluation of the esophagus: methods and value in motility disorders and GERD.
The barium esophagram is an essential component in the workup of a patient with dysphagia and gastroesophageal reflux disease, especially when considering antireflux surgery or after such surgery. The examination requires a flexible approach with an emphasis on the motility portion of the examination. When properly performed, the examination should identify the following: normal or impaired esophageal emptying; normal or abnormal motility; the presence and type of hiatal hernia; the presence of a distal stricture or mucosal ring; and in many instances, the presence of gastroesophageal reflux. In patients after antireflux surgery, the examination should identify the following: normal of impaired esophageal emptying; normal or abnormal motility; the location, tightness, and length of the fundoplication; the presence of a recurrent hernia; and the presence of gastroesophageal reflux.
Aging↗
Adrenal and sex steroid receptor evolution: environmental implications.
The nuclear receptor family responds to a diverse group of ligands, including steroids, retinoids, thyroid hormone, prostaglandins and fatty acids. Previous sequence analyses of adrenal and sex steroid receptors indicate that they form a clade separate from other nuclear receptors. However, the relationships of adrenal and sex steroid receptors to each other and to their ancestors are not fully understood. We have used new information from androgen, estrogen, mineralocorticoid and progesterone receptors in fish to better resolve the phylogeny of adrenal and sex steroid receptors. Sequence divergence between fish and mammalian steroid receptors correlates with differences in steroid specificity, suggesting that phylogeny needs to be considered in evaluating the endocrine effects of xenobiotics. Among the vertebrate steroid receptors, the most ancient is the estrogen receptor. The phylogeny indicates that adrenal and sex steroid receptors arose in a jawless fish or a protochordate and that changes in the sequence of the hormone-binding domain have slowed considerably in land vertebrates. The retinoid X receptor clade is closest to the adrenal and sex steroid receptor clade. Retinoid X receptor is noteworthy for its ability to form dimers with other nuclear receptors, an important mechanism for regulating the action of retinoid X receptor and its dimerization partners. In contrast, the adrenal and sex steroid receptors bind to DNA as homodimers. Moreover, unliganded adrenal and sex steroid receptors form complexes with heat shock protein 90. Thus, the evolution of adrenal and sex steroid receptors involved changes in protein-protein interactions as well as ligand recognition.
Animals↗
Ten criteria for effective screening: their application to multislice CT screening for pulmonary and colorectal cancers.
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Breast Neoplasms↗
Mutation of threonine-241 to proline eliminates autocatalytic modification of human carbonyl reductase.
Carbonyl reductase catalyses the reduction of steroids, prostaglandins and a variety of xenobiotics. An unusual property of human and rat carbonyl reductases is that they undergo modification at lysine-239 by an autocatalytic process involving 2-oxocarboxylic acids, such as pyruvate and 2-oxoglutarate. Comparison of human carbonyl reductase with the pig enzyme, which does not undergo autocatalytic modification, identified three sites, alanine-236, threonine-241 and glutamic acid-246, on human carbonyl reductase that could be important in the reaction of lysine-239 with 2-oxocarboxylic acids. Mutagenesis experiments show that replacement of threonine-241 with proline (T241P) in human carbonyl reductase eliminates the formation of carboxyethyl-lysine-239. In contrast, the T241A mutant has autocatalytic activity similar to wild-type carbonyl reductase. The T241P mutant retains catalytic activity towards menadione, although with one-fifth the catalytic efficiency of wild-type carbonyl reductase. Replacement of threonine-241 with proline is likely to disrupt the local structure near lysine-239. We propose that integrity of this local environment is essential for chemical modification of lysine-239, but not absolutely required for carbonyl reductase activity.
Alcohol Oxidoreductases↗
Three-dimensional model of human TIP30, a coactivator for HIV-1 Tat-activated transcription, and CC3, a protein associated with metastasis suppression.
Human TIP30 is a cofactor that specifically enhances human immunodeficiency virus-1 (HIV-1) Tat-activated transcription. The sequence of TIP30 is identical to that of CC3, a protein associated with metastasis suppression. TIP30/CC3 is a member of the short-chain dehydrogenases/reductases (SDR) family. Of the several experimentally determined SDR structures, Escherichia coli uridine diphosphate (UDP) galactose-4 epimerase is most similar to TIP30/CC3. Because the direct sequence similarity between TIP30/CC3 and E. coli UDP galactose-4 epimerase is low, we used the transitive nature of homology and employed two Aquifex aeolicus proteins as intermediaries in the homology modeling process. Comparison of our structural model with that of known SDRs reveals that TIP30/CC3 contains several well-conserved features, including a beta alpha beta fold at the amino terminus, which we predict binds NADP(H). TIP30/CC3 contains characteristic motifs at the catalytic site of SDRs, including a serine, tyrosine, and lysine that are important in catalyzing hydride transfer between substrate and cofactor. We also predict that a unique 20-amino acid sequence found at the amino terminus is an alpha-helix. Because this region contains several positively and negatively charged amino acids, it may dock TIP30/CC3 to other proteins. Our structural model points to this alpha-helix and the SDR-like part of TIP30/CC3 for mutagenesis experiments to elucidate its role in HIV-1 Tat-activated transcription, metastasis suppression, and other cellular functions.
Acetyltransferases↗
Timed barium esophagogram: A simple physiologic assessment for achalasia.
OBJECTIVE: Success of achalasia therapy is difficult to determine because repeated physiologic study is impractical and symptoms are subjective. Timed barium esophagography directly measures esophageal emptying and is simple to perform. This study (1) evaluates the assessment of myotomy by timed barium esophagography and (2) compares it with premyotomy and postmyotomy symptoms. METHODS: Fifty patients ingested 250 mL low-density barium and had upright films at 1, 2, and 5 minutes premyotomy. Forty-five underwent repeat timed barium esophagography 8 weeks (median) postmyotomy. Premyotomy and postmyotomy height and width of the barium column were compared and related to symptoms. RESULTS: At 1, 2, and 5 minutes premyotomy, median barium column height was 19, 17, and 15 cm, and width was 5.2, 4.8, and 4.5 cm, respectively. Surgery reduced these to 7.0, 5.0, and 1.0 cm and to 3.5, 3.0, and 1.0 cm, respectively (P <.001). Postmyotomy complete esophageal emptying was seen in 29%, 36%, and 49% at 1, 2, and 5 minutes. Postmyotomy height was unrelated (r approximately 0.2) to premyotomy height but was directly related to premyotomy width (r = 0.3-0.5; P <.05); postmyotomy width was directly related to premyotomy width (r approximately 0.6; P <.001). Premyotomy dysphagia was more severe when little change in width occurred from 1 to 5 minutes (r = 0.26, P =.07). Premyotomy regurgitation was more severe the higher the barium column (r approximately 0.4, P <.007). Surgery relieved symptoms in the majority of patients (grade 2-5 dysphagia from 72% to 4%, grade 2-5 regurgitation from 79% to 4%). Postmyotomy symptoms were unrelated to the timed barium esophagogram. CONCLUSIONS: (1) The timed barium esophagogram gives objective confirmation of successful myotomy. (2) Symptoms are unreliable in assessing esophageal emptying.
Barium Sulfate↗
Knowledge and attitudes of health care social workers regarding advance directives.
This cross sectional investigation describes the knowledge and attitudes of health care social workers regarding advance directives and explores factors that influence them. As major contributors to quality patient care, the level of knowledge and attitudes held by health care social workers regarding health care policy mandates are important. Mail survey methods were used to collect data from a systematic random sample (n = 324) of social workers throughout one mid-western state. Results indicate that the majority of health care social workers have high to moderate levels of knowledge about advance directives and hold positive attitudes regarding the policy. Social workers with more experience working with the elderly had higher levels of knowledge. Those employed in nursing homes and hospice settings had more positive attitudes than did those working in other health care facilities.
Adult↗
Adrenal mass evaluation in patients with lung carcinoma: a cost-effectiveness analysis.
OBJECTIVE: This study evaluates the cost-effectiveness of various imaging and biopsy strategies for characterizing adrenal masses in patients with newly diagnosed non-small cell carcinoma of the lung. MATERIALS AND METHODS: A decision-analysis model was used to compare the cost-effectiveness of nine strategies. Initial imaging included unenhanced CT using an adenoma or nonadenoma threshold of 0 or 10 H or in- and opposed-phase MR imaging. When initial imaging did not confirm an adenoma, CT-guided biopsy or subsequent imaging was performed. Medicare reimbursement was used as a surrogate of cost. Net costs were calculated as the difference in costs between two limbs of the decision tree. Net benefits were calculated as the difference between strategies and were calculated for life expectancy in years. MR imaging, CT, and biopsy accuracy, average life expectancy, and surgical mortality rates were based on the literature. RESULTS: The base case analysis determined that the most cost-effective strategy was CT with an adenoma or nonadenoma threshold of 10 H followed by MR imaging, if necessary. CT with a threshold of 0 H followed by biopsy, if necessary, was the least costly. The incremental cost-effectiveness ratio between these two strategies was $16,370 per year of life gained. CONCLUSION: Unenhanced CT using a 10 H threshold followed by MR imaging, if needed, was the most cost-effective strategy for evaluating an adrenal mass in a patient with newly diagnosed non-small cell lung cancer.
Adrenal Gland Neoplasms↗
Feasibility of instructing radiology technologists in the performance of gastrointestinal fluoroscopy.
OBJECTIVE: We sought to determine if dedicated gastrointestinal technologists could be trained to properly perform esophagography and double-contrast barium enema examinations. SUBJECTS AND METHODS: Ninety-four patients undergoing double-contrast barium enema examinations and 123 patients undergoing esophagographic examinations were included in the study. The study was conducted over a 4-month period, with examinations performed by eight gastrointestinal technologists, 10 radiology residents, and four staff radiologists. Four random lists were generated for each set of examinations. Each staff gastrointestinal radiologist, who was unaware of who had performed the examination, independently scored the representative radiographs. RESULTS: For the double-contrast barium enema examinations, no statistically significant differences were found between the technologists and residents for amount of barium used, degree of distention, cecal opacification, and quality of spot radiographs. The technologist-performed examinations had a statistically significant lower mean fluoroscopy time (3.2 min, compared with 4.0 min for staff radiologists and 5.7 min for residents). For the esophagrams, no statistically significant differences between technologists and residents were found for single-contrast esophagrams; radiographs of the gastric cardia; assessment of motility, reflux, and transit of a solid bolus; and fluoroscopy time. Double-contrast esophagrams obtained by technologists received a better mean score than did those of the residents. CONCLUSION: Radiology technologists can be trained to perform high-quality esophagography and double-contrast barium enema examinations without an unacceptably high radiation dose.
Adult↗
Imaging strategies in the pregnant cancer patient.
This review summarizes the pertinent issues of radiation exposure to the developing fetus and the existing imaging techniques available to detect neoplastic disease spread of the common malignancies in women of reproductive age (breast cancer, cervical carcinoma, Hodgkin's disease, and melanoma). The standard radiologic work-up for assessing disease extent is reviewed and the pros and cons of these various imaging modalities are discussed with regard to the potential deleterious effects on the mother and fetus. Reasonable alternatives to the standard protocols for documenting extent of disease for these neoplasms are proposed. Usually a pregnant cancer patient can be safely and reasonably staged with imaging. Magnetic resonance (MR) imaging will most often be the procedure of choice because it does not use ionizing radiation. Specialized, focused questions such as sentinel lymph node detection may require limited exposure to ionizing radiation, which will not expose the fetus to a significant dose. While a standard chest x-ray does involve ionizing radiation, it does not expose the fetus to significant radiation.
Diagnostic Imaging↗