Biomedical subjects

R Conant

Publications and source records attributed to R Conant.

At least 19 recordsLinked to original sources

PubMed2001

Radioimmunoguided imaging of prostate cancer foci with histopathological correlation.

PURPOSE: We have previously presented a technique that fuses ProstaScint and pelvic CT images for the purpose of designing brachytherapy that targets areas at high risk for treatment failure. We now correlate areas of increased intensity seen on ProstaScint-CT fusion images to biopsy results in a series of 7 patients to evaluate the accuracy of this technique in localizing intraprostatic disease. METHODS AND MATERIALS: The 7 patients included in this study were evaluated between June 1998 and March 29, 1999 at Metrohealth Medical Center and University Hospitals of Cleveland in Cleveland, Ohio. ProstaScint and CT scans of each patient were obtained before transperineal biopsy and seed implantation. Each patient's prostate gland was biopsied at 12 separate sites determined independently of Prostascint-CT scan results. RESULTS: When correlated with biopsy results, our method yielded an overall accuracy of 80%: with a sensitivity of 79%, a specificity of 80%, a positive predictive value of 68%, and a negative predictive value of 88%. CONCLUSION: The image fusion of the pelvic CT scan and ProstaScint scan helped identify foci of adenocarcinoma within the prostate that correlated well with biopsy results. These data may be useful to escalate doses in regions containing tumor by either high-dose rate or low-dose rate brachytherapy, as well as by external beam techniques such as intensity modulated radiotherapy (IMRT).

Adenocarcinoma↗

PubMed1996

Estimation of regional end-systolic wall stress during exercise in coronary artery disease.

Estimating left ventricular wall stress has recognized applications, but formulae for global stress cannot be applied to ischemic ventricles. A mathematic method for estimating regional stress in infarcted ventricles has been described. The hypothesis tested was that exercise-induced ischemia increases end-systolic wall stress. Subcostal four-chamber echocardiograms were recorded at rest and during peak symptom-limited exercise in 19 controls and 41 patients with chest pain undergoing coronary arteriography. Centerline regional wall motion and regional end-systolic wall stress were measured at rest and at peak exercise. The normal controls had increased wall motion with exercise, but wall stress remained low. All 32 of the patients with coronary artery disease (> or = 50% diameter narrowing) had wall motion abnormalities with exercise, but the sensitivity of identifying right coronary artery obstructions was poor. Patients with coronary disease had higher regional stress at peak exercise than did the controls. The sensitivity of identifying lesions in all three coronary arteries (0.95 to 1.0) was better than that for wall motion (p < 0.04). The specificity of wall stress needs to be tested in a larger population. Exercise-induced ischemia causes increased regional end-systolic wall stress that reflects its distribution in patients with coronary artery disease. These changes can be measured non-invasively during exercise echocardiography.

Case-Control Studies↗

PubMed1996

A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome.

Occipital horn syndrome (OHS), an X-linked connective tissue disorder, has recently been shown to result from mutations in the Menkes disease gene (MNK), which encodes a copper-transporting ATPase. By Southern analysis we detected a small deletion in a region 5' to the MNK gene in one patient with OHS. Genomic clones from an unaffected individual were isolated and sequenced, revealing three tandem 98 bp repeats situated upstream of the reported transcription start site, and analysis of the patient's DNA showed a deletion of one of the repeats. The deletion is likely to be responsible for the disease in this patient, as it was not observed in 110 unaffected individuals analyzed, and no other mutation in the patient was detected by RT-PCR and chemical cleavage mismatch analysis or by cDNA sequence analysis. The deletion is associated with a dramatic decrease in expression of a chloramphenicol acetyltransferase reporter gene, implicating the repeat sequences in regulation of MNK expression, although a quantitative analysis of MNK mRNA from a cell line derived from the patient shows no detectable reduction. Other experiments revealed no effect on the site of transcription initiation, termination or on splicing.

Adenosine Triphosphatases↗

PubMed1996

Preliminary imaging results using In-111 labeled CYT-356 (Prostascint) in the detection of recurrent prostate cancer.

To evaluate whether In-111 capromab pendetide (an antibody conjugate directed to a glycoprotein found primarily on the cell membrane of prostate tissue) radioimmunoscintigraphy can localize residual or metastatic prostatic carcinoma in 15 patients after prostatectomy and lymphadenectomy for prostatic carcinoma with rising serum prostate-specific antigen. One patient with 0.6 ng/ml serum prostate-specific antigen had normal imaging results and 14 patients had scintigraphic evidence of residual prostatic bed or metastatic prostatic carcinoma. Two patients with borderline abnormal bone scans had abnormal activity in the same regions on In-111 capromab pendetide images. All patients had negative radiographic abdominal and pelvic cross-sectional prestudy images, and there were no adverse effects related to In-111 capromab pendetide infusion and little human antimouse antibody response.

Antibodies, Monoclonal↗

PubMed1992

Non-radioactive detection of the most common mutations in the cystic fibrosis transmembrane conductance regulator gene by multiplex allele-specific polymerase chain reaction.

A rapid, simple, nonradioactive method for detection of four common mutations causing cystic fibrosis (CF) has been developed combining multiplexing with allele-specific polymerase chain reaction amplification. This approach (MASPCR) provides an easy assay for direct genotyping of normal and mutant CF alleles in homozygotes and heterozygotes. The strategy involves multiplex PCR of exons 10, 11, and 21 within the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a single reaction containing three common oligoprimers and either the four normal or four mutant oligos corresponding to the delta F508, G551D, G542X, and N1303K mutations. Primers are chosen so that the size of the four PCR products differ, thereby facilitating detection on agarose gels following amplification in the same reaction. Patient samples are primed with either four normal or four mutant oligo mixtures, and PCR products run in parallel on gels to detect band presence or absence. This approach provides a simple and potentially automated method for cost-effective population screening.

Alleles↗

PubMed1992

Fluorescence-based, multiplex allele-specific PCR (MASPCR) detection of the delta F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Cystic fibrosis (CF) is a common genetic disorder in Caucasians, and in some populations 70% of cases are associated with a 3 base pair (bp) deletion (delta F508) in the CFTR gene. We have implemented a fluorescence-based, multiplex allele-specific polymerase chain reaction (MASPCR) assay for deletion of the delta F508 mutation. Different allele-specific fluorescently-tagged primers are used in the PCR reaction to distinguish between normal and delta F508 alleles. Fluorescent PCR products are then visualized in a single lane on an agarose gel following electrophoresis combined with real-time multicolour fluorescence detection. The approach simplifies diagnosis of the most common mutation in the CFTR gene, and holds promise for a multiplex allele-specific, fluorescence-tagged gene amplification strategy for detection of additional CF mutations which may result in more cost-effective testing without increasing the risk of missed or erroneous diagnoses.

Alleles↗

PubMed1992

Detection of the most common mutations causing beta-thalassemia in Mediterraneans using a multiplex amplification refractory mutation system (MARMS).

A rapid, simple, cost-effective, non-radioactive method for detection of the most common mutations causing beta-thalassemia in Mediterranean people has been developed by combining multiplexing with the amplification refractory system. This approach, the multiplex amplification refractory mutation system (MARMS), provides an easy assay for direct detection of normal and mutant beta-globin genes in homozygotes and heterozygotes. The strategy involves multiplex PCR of four of the five regions of interest within the beta-globin gene in a single reaction containing a common oligoprimer and either the normal or mutant oligonucleotides corresponding to IVS-1 nucleotide 1 or IVS-1 nucleotide 6, IVS-1 nucleotide 110, codon 39, and IVS-2 nucleotide 1 regions. Primers are chosen so that the sizes of the four PCR products differ, thereby facilitating detection on agarose gels following amplification. Patient samples are primed with either four normal or four mutant oligonucleotide mixtures and the common oligoprimer, and PCR products run in parallel on gels to detect band presence or absence. This approach simplifies mutation detection and shows promise for automation employing fluorescent-tagged primers.

Alleles↗

PubMed1989

Effect of long-term high intensity aerobic training on left ventricular volume during maximal upright exercise.

The purpose of this study was to determine whether high intensity, long-term aerobic training causes the left ventricle to develop different mechanisms for increasing cardiac output during submaximal and maximal upright bicycle exercise. Fifteen competitive collegiate long distance runners and 14 healthy sedentary adults were studied with use of subcostal view four chamber two-dimensional echocardiography at rest and during and at peak maximal upright bicycle exercise. At rest, the athletes had a larger end-diastolic volume index (85 +/- 14 ml/m2) (mean +/- 1 SD) than that of the sedentary adults (62 +/- 14 ml/m2) and a larger end-systolic volume index (37 +/- 11 versus 21 +/- 6 ml/m2). During low and moderate intensity exercise, end-diastolic and stroke volume indexes increased in both groups, but at high intensity exercise and at peak exercise the end-diastolic volume index of both groups decreased significantly below rest value (athletes, 61 +/- 14; sedentary subjects, 46 +/- 10 ml/m2, both p less than 0.001 compared with rest). Reflecting the decreased end-diastolic volume index, at peak exercise, the stroke volume index had decreased from intermediate exercise values in both groups and was not different from rest values. Therefore, although long distance runners have a dilated left ventricle at rest, they utilize the same mechanisms as sedentary adults for increasing cardiac output during upright dynamic exercise. At low and moderate level exercise, the Frank-Starling mechanism is a dominant mechanism for increasing cardiac output, but at peak exercise, probably because of reduced diastolic left ventricular filling, enhanced contractility is the major mechanism for maintaining stroke volume.

Adult↗

PubMed1989

Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans.

Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20 inferior, nine non-Q wave infarcts), for measurement of left ventricular mass and ejection fraction. The left ventricular mass index increased from 94 +/- 30 to 118 +/- 27 g/m2 (p less than 0.01) during the time of the two studies. There was a significant correlation between the change in left ventricular mass index and improved resting ejection fraction (r = 0.48, p less than 0.001) and exercise ejection fraction (r = 0.48, p less than 0.001) at the follow-up study. Of the 32 patients who increased their left ventricular mass index greater than 7%, 18 improved their rest ejection fraction greater than 0.05 units and 17 improved their exercise ejection fraction greater than 0.05 units. Conversely, of the 13 patients who failed to increase their left ventricular mass index, only three improved their rest ejection fraction and one improved the exercise ejection fraction (Fisher's exact test, p less than 0.05). We reached three conclusions. First, in humans, significant hypertrophy of the noninfarcted myocardium can be detected by two-dimensional echocardiography, 9 months postmyocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Quantitative analysis of segmental wall motion during maximal upright dynamic exercise: variability in normal adults.

Twenty-five healthy adults underwent subcostal-view, four-chamber two-dimensional echocardiographic examination while upright at rest and at the peak of maximal bicycle exercise. The purpose of the study was to determine whether the variability in regional left ventricular endocardial motion, previously demonstrated to be present at rest, persisted at peak exercise. The rest and exercise end-diastolic and end-systolic endocardial contours were visually identified, digitized, and divided into 32 radial segments after realignment by the computer. At rest there was similar percent segmental area reduction for the septum (segments 1 to 12) (54 +/- 4%, mean +/- 1 SD), apex (segments 13 to 20) (67 +/- 3%), and lateral wall (segments 21 to 32) (67 +/- 8%). At peak exercise the percent area reduction increased significantly: septum 84 +/- 5%, apex 88 +/- 2%, lateral wall 83 +/- 6% (p less than .001 compared with rest for all areas). However, there was considerable variability in percent area reduction between different radial segments in the same individual. At rest the difference between minimal and maximal percent area reduction within the same individual was 49 +/- 17 percentage units (range 21 to 83) and that at peak exercise was 32 +/- 17 percentage units (range 0 to 66). It is concluded that, because the range of standard deviation of normal endocardial motion and the degree of variability between radial segments in the same healthy individual are significant, qualitatively determined "hypokinesis," as commonly assessed clinically, may be a normal event. However, segmental akinesis or dyskinesis, which occurred rarely at rest and never at peak exercise, must be considered abnormal events.

Adolescent↗

PubMed1985

The allyl group for protection in carbohydrate chemistry. 17. Synthesis of propyl O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3- di-O-methyl-alpha-L-rhamnopyranosyl)-(1----2)-3-O-methyl-alpha- L-rhamnopyranoside: the oligosaccharide portion of the major serologically active glycolipid from Mycobacterium leprae.

Allyl 4-O-benzyl-alpha-L-rhamnopyranoside was converted into allyl 4-O-benzyl-3-O-methyl-alpha-L-rhamnopyranoside and this was condensed with 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl chloride to give a disaccharide derivative which was converted into allyl 4-O-benzyl-2-O-(2,3-O-isopropylidene-alpha-L-rhamnopyranosyl)-3-O-methyl -alpha- L-rhamnopyranoside. This disaccharide derivative was condensed with 2,4-di-O-acetyl-3,6-di-O-methyl-alpha-D-glucopyranosyl chloride to give a trisaccharide derivative which was converted into the title compound. This compound represents the oligosaccharide portion of the major serologically active glycolipid from Mycobacterium leprae which is required to prepare a synthetic diagnostic agent for leprosy infection at an early stage and to investigate the specificities of monoclonal antibodies directed towards the glycolipid.

Glycolipids↗

PubMed1984

Exercise subcostal two-dimensional echocardiography: a new method of segmental wall motion analysis.

This study determines the effectiveness of the subcostal view 2-dimensional (2-D) echocardiogram in providing images of left ventricular wall motion at rest and during symptom-limited upright bicycle exercise, and compares 2-D echocardiographic regional wall motion analysis with first-pass radionuclide angiography. Diagnostic-quality subcostal 2-D echocardiograms at rest were obtained in 95% of unselected persons studied (16 of 17 normal subjects and 23 of 24 patients who had had myocardial infarction [MI] ). All who had adequate studies at rest had diagnostic-quality maximal exercise studies. Segmental wall motion at rest and exercise determined by 2-D echocardiography correlated well with radionuclide angiography in both the normal and post-MI groups. The chi-squared values for the 3 segments analyzed were: anterior 52 (p less than 0.001), apical 56 (p less than 0.001) and inferior 37 (p less than 0.001). It is concluded that subcostal view 2-D echocardiography at rest and at the peak of symptom-limited upright bicycle exercise is a feasible and accurate noninvasive method for the analysis of segmental left ventricular function.

Adult↗

PubMed1984

Noninvasive measurement of the rest and exercise peak systolic pressure/end-systolic volume ratio: a sensitive two-dimensional echocardiographic indicator of left ventricular function.

Thirty-five patients with previous myocardial infarction and 25 normal subjects underwent subcostal view two-dimensional echocardiography at rest and at peak up-right bicycle exercise. The purpose was to assess changes in left ventricular volume with maximal upright bicycle exercise and to compare the utility of the peak systolic pressure/end-systolic volume index ratio and ejection fraction as indicators of left ventricular function. With exercise, normal subjects had a decrease in end-systolic volume index (22 +/- 8 to 11 +/- 3 ml/m2) (p less than 0.001); the normal ejection fraction (59 +/- 9 to 72 +/- 8%, p less than 0.001) and the pressure/volume ratio (6 +/- 3 to 18 +/- 6, p less than 0.001) increased. In patients with prior myocardial infarction there was no change in end-systolic volume index, ejection fraction or pressure/volume ratio with exercise. Although at peak exercise significant differences between normal subjects and patients with prior infarction were demonstrated in end-systolic volume index (p less than 0.001), ejection fraction (p less than 0.001) and pressure/volume ratio (p less than 0.001), the pressure/volume ratio provided sharper delineation between the two groups than did ejection fraction. The exponential relation of the pressure/volume ratio and ejection fraction at peak exercise demonstrates that the pressure/volume ratio is more sensitive as an indicator of normal or borderline left ventricular function and that ejection fraction is more sensitive in quantifying the degree of left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1979

Effects of maximal exercise stress on left ventricular function in patients with coronary artery disease using first pass radionuclide angiocardiography: a rapid, noninvasive technique for determining ejection fraction and segmental wall motion.

Angiographically determined changes in segmental wall motion (SWM) and ejection fraction (EF) are sensitive indices of left ventricular (LV) function. To compare the effects of exercise on LV function, first pass radionuclide angiocardiography was used before and during maximal upright bicycle stress in patients with nonsignificantly stenosed coronary arteries, and in those with greater than 75% stenosis. Gamma camera acquisitions were made in the 30 degree RAO projection using a 20 mCi I.V. bolus of 99mTc-pertechnetate. In the control group (seven normals, one nonsignificant (CAD) the EF significantly increased between rest and exercise (0.65 +/- 0.03 to 0.81 +/- 0.03 (mean +/- SEM), p less than 0.005). In this group SWM measured over the two anterior and two inferoposterior segments uniformly increased. In the 11 patients with a history of angina and significant coronary artery obstruction, the EF did not change in three and significantly decreased in the remaining eight (0.57 +/- 0.04 to 0.45 +/- 0.03, p less than 0.005). In all 11 patients SWM either decreased or did not increase in the areas supplied by the significantly stenosed coronary arteries. Upright maximal stress angiocardiography appears to be well-suited for diagnosing ischemic heart disease and localizing the area of ischemic dysfunction.

Adult↗

PubMed1977