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Biomedical subjects

C Sanders

Publications and source records attributed to C Sanders.

At least 55 records · Page 3Linked to original sources

Current role of conventional and digital aortography in the diagnosis of aortic disease.

The availability of the less invasive techniques such as CT, MRI, and digital angiography require reexamination of the indications for conventional screen-film aortography. Because of poor image quality, IV digital subtraction angiography should be limited to congenital aortic disease and follow-up cases. Intraarterial digital angiography can be used as a supplement to or as a replacement for conventional aortography in most cases. Care should be used in substituting intraarterial digital angiography for conventional studies in aortic dissection and aortic rupture; continuing problems with digital subtraction artifacts may introduce error in cases with subtle abnormalities. In aortic aneurysm, CT is usually sufficient for diagnosis and surgical planning with angiography used for inconclusive examinations or more accurate determination of branch involvement. CT is the primary diagnostic examination in suspected chronic or subacute dissection and is the method of choice in sequential studies of patients following medical or surgical therapy for dissection. In acute aortic dissection, either angiography or CT may be used and are equally diagnostic. Angiography is most helpful in aortic dissection with suspected brachiocephalic vessel involvement, coexistant coronary artery disease, or in cases of indeterminate CT. In blunt chest trauma, aortography remains the examination of choice in the diagnosis of aortic transection. CT may play a role in excluding aortic damage in stable patients with a low clinical suspicion of aortic transection.

Acute Disease↗

Upper respiratory tract infection in children, domestic temperatures, and humidity.

STUDY OBJECTIVE: The aim of the study was to seek for a possible association between the incidence of upper respiratory tract infections and air temperature and humidity in the home. DESIGN: Recordings of temperature and relative humidity were made in living rooms and children's bedrooms over a six month period and related to incidence of upper respiratory tract infection. SETTING: The study was carried out in one general practice of 10,000 patients. PATIENTS: 297 children aged 24-59 months were studied, selected in random order from the practice age-sex register. MEASUREMENTS AND MAIN RESULTS: Temperature and humidity recordings were made with thermohygrograph recorders over six days. Upper respiratory tract infections were recorded (a) retrospectively over the previous 12 months, and (b) during the study period. Past history of acute otitis media and recent family history of respiratory infection were also obtained. No significant association was found between the variables, although the bedrooms of children with reported upper respiratory tract infections were cooler overnight than those of non-infected children (mean difference 0.8 degrees C, 95% confidence limits 0.7 degrees C). No association was found between reported or recorded upper respiratory tract infections and age or type of home, family size, level of occupancy, social class, or smoking habits. Only 15 children (5%) were identified by their parents as having had asthma, but 58 (19.5%) had had a "wheezy chest". A greater proportion of children who wheezed slept in cooler bedrooms, had gas fires rather than central heating, and had more smokers in the house. CONCLUSIONS: No association between upper respiratory tract infection and domestic temperature or humidity levels could be shown in this study. Since dampness is repeatedly presented as a health risk, further study is required.

Child, Preschool↗

Vitamin K-dependent carboxylase: influence of the "propeptide" region on enzyme activity.

The liver microsomal vitamin K-dependent carboxylase catalyzes the post-translational conversion of specific glutamyl to gamma-carboxyglutamyl (Gla) residues in precursor forms of a limited number of proteins. These proteins contain an amino-terminal extension (propeptide) that is presumed to serve as an enzyme recognition site to assure their normal processing. The free, noncovalently bound propeptide has also been shown to stimulate the in vitro activity of this enzyme. This peptide has now been shown to lower the app Km of a low-molecular-weight Glu site substrate while having no influence on the app Km of the other substrates, vitamin KH2, O2, and CO2/HCO3-. Propeptide addition was shown to have no influence on the ratio of the two products of the enzyme, Gla and vitamin K-2,3-epoxide. Stimulation of carboxylase activity by the propeptide from human factor X was observed in a number of rat tissues and in the liver of a number of different species. Stability of the enzyme in crude microsomal preparations was greatly enhanced by the presence of propeptide. These observations are consistent with the hypothesis that this region of the protein substrates for the carboxylase not only serves an enzyme recognition or docking function but also modulates the activity of the enzyme by altering the affinity for one of its substrates.

Amino Acid Sequence↗

A comparison of dual-energy digital radiography and screen-film imaging in the detection of subtle interstitial pulmonary disease.

An ROC study is described which compares the performance of three types of images--conventional screen-film, single-energy digital and dual energy bone cancelled (soft tissue) digital--in detecting subtle interstitial pulmonary disease. Marginally detectable nodular and reticulonodular patterns (12 different patterns of each) were superimposed over the lungs of a frozen human chest phantom to simulate the clinical situation. The digital images were formatted on film at full size (ie, 35 cm X 43 cm). A total of 156 images (52 of each type, of which 28 were normal and 24 had simulated pathology) were used in the study and read by five experienced chest radiologists. Using a paired t-test, the areas under the individual ROC curves were compared for three combinations of images--single-energy digital and conventional, soft tissue digital and conventional, and soft tissue and single-energy digital. No statistically significant difference was observed between the conventional and single-energy digital images. The readers performed better with both conventional and single-energy digital images than with the soft tissue digital images at statistically significant levels (P = 0.05 for conventional vs. soft tissue digital and P = 0.02 for single-energy digital vs. soft tissue digital). The results suggest that there is no advantage in employing dual-energy soft tissue images to assist in diagnosing interstitial disease in the clinical setting. They also suggest that spatial resolution requirements are less demanding in digital chest systems that obtain scatter-free images than in digital systems utilizing conventional scatter control techniques.

Evaluation Studies as Topic↗

Digital imaging of the chest.

During the past several years, image acquisition in nuclear medicine, computed tomography, ultrasonography, subtraction angiography, and magnetic resonance has been by digitization. Despite these advances, research in the development of digital imaging in conventional radiography has lagged behind. Although studies with a variety of digital techniques have been carried out on several fronts, we still do not possess a method that has captured the imagination of the majority of radiologists and other physicians to a point where it could replace conventional screen-film imaging. This article reviews the current status and general principles of the technology, focusing on the four digital radiographic techniques that have shown the greatest promise - film digitization, an image intensifier - based system, photostimulable phosphor plates, and a scanned projection system. The physical aspects of each of the four systems and the clinical results that have been reported to date, as well as the advantages and disadvantages of each system, are presented.

Humans↗

Fluorescence from pyrene-labeled native and reconstituted chicken gizzard tropomyosins.

Sulfhydryl groups at Cys-36 on the beta chain and at Cys-190 on the gamma chain of chicken gizzard tropomyosin were reacted with the pyrene-containing sulfhydryl-specific reagents N-(1-pyrenyl)iodoacetamide and N-(1-pyrenyl)maleimide. Tropomyosin prepared and labeled under nondenaturing conditions displayed significant pyrene monomer emission but low levels of pyrene excimer fluorescence. In contrast, tropomyosin subjected to denaturation and renaturation prior to labeling, or labeled in the denatured state prior to renaturation, displayed considerable excimer emission. Furthermore, labeling of isolated beta or gamma chains in denaturant, followed by reconstitution, gave separate samples of beta beta- and gamma gamma-tropomyosin that exhibited even greater pyrene excimer to monomer emission ratios. As pyrene excimers can form only when an excited pyrene is immediately adjacent to a ground state pyrene, i.e., when the labeled Cys residues on the two chains in a tropomyosin coiled coil share the same cross section, these results support conclusions based upon chemical crosslinking studies [C. Sanders, L. D. Burtnick, and L. B. Smillie (1986) J. Biol. Chem. 261, 12774-12778] that native gizzard tropomyosin exists predominantly as a beta gamma-heterodimer. In addition, the low degree of labeling of native gizzard tropomyosin and the differences in degrees of labeling of beta beta- and gamma gamma-tropomyosins in the absence of denaturants reflect on the accessibilities of the sulfhydryl groups in these tropomyosin isoforms. Circular dichroism measurements indicate that the labeled proteins form stable coiled coil structures that have thermal stabilities comparable to that of the native protein.

Affinity Labels↗

Comparison of the structure and dynamics of chicken gizzard and rabbit cardiac tropomyosins: 1H NMR spectroscopy and measurement of amide hydrogen exchange rates.

The side chain and backbone mobilities of chicken gizzard tropomyosin (TM) and its nonpolymerizable derivative have been investigated by H NMR spectroscopy and amide hydrogen exchange kinetics and compared to those of rabbit cardiac TM and its nonpolymerizable derivative. Analysis of the 300-MHz H NMR spectra of native chicken gizzard and rabbit cardiac TMs and their nonpolymerizable derivatives showed that the line widths of the aromatic and histidine residues were within a factor of 2 for all four proteins, demonstrating that the side chain mobility of these residues is similar in the different TMs. Direct proton exchange-out kinetics were determined in D2O in the pD range 1.5-3.0 at 25 degrees C by H NMR spectroscopy. Multiple exponential fitting of the exchange data indicated the presence in gizzard TM of at least three kinetically distinct classes of amide hydrogens at pD 1.7 with average population sizes of 147, 74, and 61, whose rates were retarded by a factor of 10, 10(3), and 10(5), respectively, relative to the random-coil peptide poly(DL-alanine). Measurement of the direct exchange kinetics of both rabbit cardiac and nonpolymerizable gizzard TMs showed that their rate constants and population sizes were within experimental error of those for the gizzard protein, except that the fast exchanging class for cardiac TM was increased in size while that of the nonpolymerizable gizzard TM was reduced, relative to that for gizzard TM. Comparison of the exchange-out kinetics for the cardiac and gizzard proteins at pH 2.0 and 55 degrees C, where only the two slowly exchanging amide hydrogen sets are measured, again demonstrated the similarity of their kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗

In vitro chemosensitivity of brain tumors to cisplatin and its analogues, iproplatin and carboplatin.

The human tumor stem-cell assay was used to investigate the in vitro chemosensitivity of 27 evaluable samples to cisplatin and its analogues, iproplatin and carboplatin, as well as to BCNU, teniposide, vindesine, and dibromodulcitol. All agents exhibited some antitumor activity with the exception of dibromodulcitol (zero response out of 19 evaluable samples). Vindesine, BCNU, and carboplatin were the three most active compounds, with response rates of 29%, 23%, and 22%, respectively. There was a lack of complete cross-resistance between carboplatin and cisplatin as well as between carboplatin and BCNU. Our data suggest that clinical studies with carboplatin and combinations of vindesine plus cisplatin and its analogues may be worthwhile.

Brain Neoplasms↗

Myocardial calcification and cardiac dysfunction in chronic renal failure.

PURPOSE: Myocardial calcium content may have clinical importance in end-stage renal disease (ESRD), but it is difficult to detect during life. Our goal was to assess the effect of myocardial calcium content on left ventricular ejection fraction (LVEF) in uremic patients undergoing dialysis. PATIENTS AND METHODS: Energy subtraction radiography of the chest was used to measure myocardial calcium content in 43 patients undergoing dialysis, in 32 control subjects, and in nine patients with advanced cardiomyopathy. LVEF and left ventricular end-diastolic dimension were measured by two-dimensional echocardiography. The concentration of parathyroid hormone was measured by radioimmunoassay; calcium-phosphorus product, alkaline phosphatase, and serum bicarbonate were also assessed. RESULTS: Patients undergoing dialysis had a greater myocardial calcium content than control subjects [262 +/- 15.4 (mean +/- SE) versus 187 +/- 8 mg/cm2, p less than 0.05]. Ten patients with the highest myocardial calcium content (Group I) had the lowest LVEF values and highest left ventricular end-diastolic dimension. Significant inverse linear associations between LVEF and myocardial calcium content (r = -0.425, p = 0.013) and between parathyroid hormone concentration and LVEF (r = -0.352, p = 0.047) were noted. There was no association between parathyroid hormone concentration and myocardial calcium content. Stepwise regression analysis showed a strong positive correlation between myocardial calcium content and calcium-phosphorus product, vascular calcification, race (black), and parathyroidectomy. Similar analysis shows that LVEF was significantly associated with myocardial calcium content, lung calcium, calcium-phosphorus product, and race (black). CONCLUSION: We suggest that increased myocardial calcium content results from poor calcium and phosphorus control and may be enhanced by parathyroid hormone hyperactivity. Increased myocardial calcium content is strongly associated with myocardial dysfunction in patients undergoing dialysis.

Adult↗

Detection of emphysema with computed tomography. Correlation with pulmonary function tests and chest radiography.

We studied 60 male patients who had concurrent chest films (CXR), computed tomography scans (CT) and pulmonary function tests (PFT) to assess the sensitivity of CT and conventional films in detecting emphysema compared with PFT. We also sought to determine whether emphysema could be diagnosed by CT in patients with normal pulmonary function. Using a method similar to that proposed by Bergin, we scored the severity of emphysema depicted by CT, and using arterial deficiency and bullae as criteria, we estimated the degree of emphysema on CXR. There was a significant inverse correlation between CT scores for emphysema and percentage predicted values of DLco/VA (r = -0.650), FEV1 (r = -0.552), and FVC (r = -0.409), (P less than 0.001). A significant but smaller correlation also was noted with the CXR scores and percentage predicted: DLco/VA (r = -0.564), FEV1 (r = -0.454), and FVC (r = -0.355), (P less than 0.005). When decreased diffusion capacity and airway obstruction were used as functional criteria of emphysema, CT was as sensitive as PFT and more sensitive than CXR in detecting emphysema (96% vs. 68%). There was CT evidence of emphysema in 69% (24/35) of patients who did not have functional findings of emphysema. In 12 pathologic specimens available for review, 11 had emphysema by CT and pathologic examination; one patient had centrilobular emphysema undetected by CT. We conclude that CT is as sensitive as PFT in detecting emphysema and more sensitive than conventional radiography. CT may be more sensitive than PFT in detecting mild emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Percutaneous fine needle aspiration in the diagnosis and management of mediastinal cysts in adults.

Management of asymptomatic mediastinal cysts in adults is controversial. In the past, these cysts were excised primarily to establish a diagnosis. Presently, computerized tomography (CT) of the chest can diagnose the majority of mediastinal cysts, based on their smooth contour and low density; however, CT diagnosis of a mediastinal cyst based on density can be erroneous. In six patients, we established the diagnosis of mediastinal cyst by percutaneous needle biopsy (PNB) without complication. In four of the patients, PNB was done as an outpatient procedure. Follow-up in five patients ranged from three months to three years, with no increase in the size of the cyst; in the sixth patient, surgical excision showed a hygroma. Thus, diagnosis of a mediastinal cyst can be safely confirmed by PNB. We suggest that these asymptomatic patients can be followed up without the need for surgical excision.

Adult↗

Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome.

Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies.

Acquired Immunodeficiency Syndrome↗

Comparison of cell cultures for rapid isolation of enteroviruses.

Cell culture isolation is still the most reliable method for the detection of enteroviruses from clinical specimens. Rapid diagnosis of enterovirus infection affects patient management. To increase yield and enhance the rapidity of enterovirus isolation in cell cultures, we used Buffalo green monkey kidney (BGM) cells and subpassages of primary human embryonic kidney (HEK) cells in addition to the human diploid fibroblast (MRC-5) cells and primary cynomolgus or rhesus monkey kidney (MK) cells routinely used for enterovirus culturing. Growth characteristics of enteroviruses from 421 specimens were studied. All specimens were cultured in MRC-5, MK, and BGM cells, and 204 of these specimens were also cultured in HEK cells. Forty-two percent of the enteroviruses became positive within 3 days, and 85% did so within 7 days. MRC-5 cells provided the highest yield of enteroviruses overall and were the best cell type for the recovery of poliovirus and echovirus. MK cells provided the second best yield but were more useful than MRC-5 cells for coxsackievirus. BGM cells supported the growth of additional isolates of coxsackievirus and enhanced the speed of isolation. HEK cells supported the growth of additional isolates of both coxsackievirus and echovirus, but subculturing was always required for definite enterovirus cytopathic effects. The recovery rate increased 11% when two additional cell lines were used. The use of two tubes of MK cells significantly increased the yield of all enterovirus types. We conclude that the use of multiple appropriate cell lines increases yield and enhances the rapidity of enterovirus isolation.

Animals↗

Atrial septal defect in older adults: atypical radiographic appearances.

Atrial septal defect (ASD) is the most common congenital cardiac anomaly manifested in adulthood. Clinical and radiographic features are well defined in patients less than 30 years of age. In older patients, however, the clinical symptoms are often atypical, and the auscultatory findings may be misleading. The radiographic manifestations in older patients have not been well described. In the current study, of 70 patients over the age of 50 years with proved ASD, 21 (30%) had atypical radiographic features, including apparently normal vascularity, left atrial enlargement, pulmonary venous hypertension, and pulmonary edema. In a control group of 70 younger patients with ASD, only 5.7% had atypical findings. The development of pulmonary venous hypertension and pulmonary edema in older patients was associated with smaller defects and a higher prevalence of mitral valve disease, left ventricular dysfunction, and pulmonary arterial hypertension than seen in older patients with typical radiographic findings.

Age Factors↗