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Biomedical subjects

J R Corbett

Publications and source records attributed to J R Corbett.

At least 19 recordsLinked to original sources
PubMed2000

Attenuation corrected cardiac perfusion SPECT.

Image artifacts, especially those caused by photon attenuation, commonly affect the specificity of cardiac SPECT perfusion imaging. Although often suspected by characteristic patterns identified in female and male patients respectively, the widely variable body habitus of individual patients are associated with unpredictable variations in tissue attenuation. The accuracy of PET perfusion imaging has long benefited from correction methods for soft tissue attenuation. This paper reviews recent developments in attenuation correction methods for cardiac SPECT perfusion imaging. Several commercial methods are now available. Initial reports indicate these methods have varied greatly in their clinical success. Some methods have demonstrated significant improvements. However, others have created more artifacts than they have cured. Recent developments suggest very significant clinical advantages can be achieved with robust, well-validated methods for attenuation corrected SPECT in the diagnostic evaluation of coronary heart disease, high risk coronary disease, and women.

Artifacts↗
PubMed1999

Fatty acids for myocardial imaging.

Radioiodinated free fatty acids are tracers that can be used to assess both myocardial perfusion and metabolism. There have been several fatty acids and structurally modified fatty acids studied since Evans' initial report of radiolabeled I-123 oleic acid in 1965. The radiolabeling of a phenyl group added to the long chain fatty acids in the omega-terminal position opposite the carboxyl terminal group prevents nonspecific deiodination and the rapid release of free iodine as the tracer undergoes beta-oxidation. The additional inclusion of a methyl or dimethyl group to the chain slows oxidation resulting in prolonged myocardial retention. The longer retention of the radiolabel permits longer image acquisitions more compatible with single photon emission computed tomography (SPECT) imaging, especially with single-detector imaging systems. Several protocols have been implemented using these compounds, particularly 15-(para-iodophenyl)-3-R,S-methyl pentadecanoic BMIPP, to detect abnormal fatty acid metabolism in ischemic heart disease as well as in nonischemic and hypertrophic cardiomyopathies. Successful management of patients with ischemic cardiomyopathies depends on the accurate identification of hibernating myocardium. The studies covered in this review suggest that both IPPA and BMIPP, especially when combined with markers of myocardial perfusion, may be excellent tracers of viable and potentially functional myocardium. Future studies with larger numbers of patients are needed to confirm the results of these studies and to compare their efficacy with that of other available imaging modalities. Cost and distribution issues will have to be resolved for these metabolic tracers to compete in the commercial marketplace. Otherwise they will likely be available only on a limited basis for research use. As progress is made with these issues and with the development of newer imaging systems, the use of radioiodinated and fluorinated fatty acids is likely to be increasingly attractive.

Cardiomyopathy, Hypertrophic↗
PubMed1999

Sensitivity of [11C]phenylephrine kinetics to monoamine oxidase activity in normal human heart.

UNLABELLED: Phenylephrine labeled with 11C was developed as a radiotracer for imaging studies of cardiac sympathetic nerves with PET. A structural analog of norepinephrine, (-)-[11C]phenylephrine (PHEN) is transported into cardiac sympathetic nerve varicosities by the neuronal norepinephrine transporter and stored in vesicles. PHEN is also a substrate for monoamine oxidase (MAO). The goal of this study was to assess the importance of neuronal MAO activity on the kinetics of PHEN in the normal human heart. MAO metabolism of PHEN was inhibited at the tracer level by substituting deuterium atoms for the two hydrogen atoms at the alpha-carbon side chain position to yield the MAO-resistant analog D2-PHEN. METHODS: Paired PET studies of PHEN and D2-PHEN were performed in six normal volunteers. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were measured in venous samples taken during the 60 min dynamic PET study. Myocardial retention of the tracers was regionally quantified as a retention index. Tracer efflux between 6 and 50 min after tracer injection was fit to a single exponential process to obtain a washout half-time for all left ventricular regions. RESULTS: Although initial heart uptake of the two tracers was similar, D2-PHEN cleared from the heart 2.6 times more slowly than PHEN (mean half-time 155+/-52 versus 55+/-10 min, respectively; P < 0.01). Correspondingly, heart retention of D2-PHEN at 40-60 min after tracer injection was higher than PHEN (mean retention indices 0.086+/-0.018 versus 0.066+/-0.011 mL blood/ min/mL tissue, respectively; P < 0.003). CONCLUSION: Efflux of radioactivity from normal human heart after uptake of PHEN is primarily due to metabolism of the tracer by neuronal MAO. Related mechanistic studies in the isolated rat heart indicate that vesicular storage of PHEN protects the tracer from rapid metabolism by neuronal MAO, suggesting that MAO metabolism of PHEN leaking from storage vesicles leads to the gradual loss of PHEN from the neurons. Thus, although MAO metabolism influences the rate of clearance of PHEN from the neurons, MAO metabolism is not the rate-determining step in the observed efflux rate under normal conditions. Rather, the rate at which PHEN leaks from storage vesicles is likely to be the rate-limiting step in the observed efflux rate.

Adult↗
PubMed1998

Resting coronary flow and coronary flow reserve in human infants after repair or palliation of congenital heart defects as measured by positron emission tomography.

OBJECTIVE: Coronary physiology in infants with congenital heart disease remains unclear. Our objective was to better understand coronary physiology in infants with congenital heart disease. METHODS: We used positron emission tomography with nitrogen 13-labeled ammonia to measure myocardial perfusion at rest and with adenosine (142 micrograms/kg/min x 6 minutes) in five infants after anatomic repair of a congenital heart lesion (group I), and in five infants after Norwood palliation for hypoplastic left heart syndrome (group II). The groups were matched for age, weight, and time from the operation. RESULTS: Resting coronary flow in the left ventricle in group I was 1.8 +/- 0.2 ml/min/gm; resting flow in the right ventricle in group II was 1.0 +/- 0.3 ml/min/gm (p = 0.003). Coronary flow with adenosine was 2.6 +/- 0.5 ml/min/gm in group I and 1.5 +/- 0.7 ml/min/gm in group II (p = 0.02). Absolute coronary flow reserve was the same in both groups (1.5 +/- 0.2 in group I vs 1.6 +/- 0.3 in group II, p = 0.45). Oxygen delivery was reduced in group II compared with group I at rest (16.1 +/- 4.2 ml/min/100 gm vs 28.9 +/- 4.42 ml/min/100 gm, p = 0.02) and with adenosine (25.5 +/- 8.1 ml/min/100 gm vs 42.3 +/- 5.8 ml/min/100 gm, p = 0.02). CONCLUSIONS: Infants with repaired heart disease have higher resting flow and less coronary flow reserve than previously reported for adults. After Norwood palliation, infants have less perfusion and oxygen delivery to the systemic ventricle than do infants with a repaired lesion. This may in part explain why the outcome for patients with Norwood palliation is less favorable than for others.

Adenosine↗
PubMed1996

Simultaneous transmission/emission myocardial perfusion tomography. Diagnostic accuracy of attenuation-corrected 99mTc-sestamibi single-photon emission computed tomography.

BACKGROUND: The purpose of the present study was to assess the diagnostic performance of attenuation-corrected (AC) stress 99mTc-sestamibi cardiac single-photon emission computed tomography (SPECT) for the identification of coronary heart disease (CHD). METHODS AND RESULTS: With a triple-detector SPECT system with a 241Am transmission line source, simultaneous transmission/emission tomography (TCT/ECT) was performed on 60 patients with angiographic coronary disease and 59 patients with < or = 5% likelihood of CHD. Iteratively reconstructed AC stress 99mTc-sestamibi perfusion images were compared with uncorrected (NC) filtered-backprojection images. Normal database polar maps were constructed from AC and NC images for quantitative analyses. From the low-likelihood patients, the visual and quantitative normalcy rates increased from 0.88 and 0.76 for NC to 0.98 and 0.95 for AC (P < .05). For the detection of CHD, the receiver operating characteristic curves for the AC images demonstrated improved discrimination capacity (P < .05), and sensitivity/specificity values increased from 0.78/0.46 (NC) to 0.84/0.82 (AC) with visual analysis and from 0.84/0.46 (NC) to 0.88/0.82 (AC) with quantitative analysis. For localization of stenosed vessels, visual and quantitative sensitivity values were 0.51 and 0.63 for NC and 0.64 and 0.78 for AC images (P < .05), respectively. CONCLUSIONS: TCT/ECT myocardial perfusion imaging significantly improves the diagnostic accuracy of cardiac SPECT for the detection and localization of CHD. Clinical use of TCT/ECT imaging deserves serious consideration.

Coronary Angiography↗
PubMed1996

Lymphangioma circumscriptum associated with paravesical cystic retroperitoneal lymphangioma.

A boy with long-standing congenital cutaneous lymphangioma circumscriptum (LC), presented at the age of 6 years with an episode of painless haematuria, subsequently attributed to bladder wall involvement of a paravesical cystic retroperitoneal lymphangioma. Magnetic resonance imaging demonstrated this lymphangioma to be in communication with the cutaneous lesions. Deep lymphatic and visceral involvement is an extremely unusual occurrence in association with LC. This is the first report of an association between LC and cystic retroperitoneal lymphangioma. LC occasionally heralds a deeper, more clinically significant lymphangioma which may not become apparent until many years after the initial dermatological presentation. We report this case to raise awareness of this potential association and to demonstrate the usefulness of magnetic resonance imaging in the assessment of the deep component of cutaneous lymphangiomas.

Child↗
PubMed1996

Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons.

UNLABELLED: The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. METHODS: Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. RESULTS: No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. CONCLUSION: PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.

Adult↗
PubMed1995

Detection of alterations in left ventricular fatty acid metabolism in patients with acute myocardial infarction by 15-(p-123I-phenyl)-pentadecanoic acid and tomographic imaging.

15-(p-iodine 123-phenyl)-pentadecanoic acid (IPPA) is a synthetic radiolabeled fatty acid with kinetics similar to palmitate. Fourteen patients who had had an acute myocardial infarction 7 +/- 6 days earlier and 9 normal volunteers were studied after being injected with IPPA. The volunteers were remarkable for homogeneous uptake and metabolism of IPPA; 13 of 14 infarct patients showed areas of decreased uptake > 2 SDs below the mean of the volunteers. Metabolism was homogeneous in the volunteers (14.2% +/- 5.8%) and was significantly higher than in regions identified as infarcted (3.9% +/- 12.1%, p < 0.001). Noninfarcted regions in the patients demonstrated significantly increased rates of IPPA metabolism compared to rates in volunteers (23.0% +/- 9.6% p < 0.001). We conclude that patients with recent myocardial infarction have abnormalities of fatty acid metabolism such as decreased uptake and clearance of fatty acid in regions of infarction and normal uptake but relatively increased fatty acid clearance in unaffected regions of the myocardium.

Adult↗
PubMed1995

Simultaneous transmission-emission thallium-201 cardiac SPECT: effect of attenuation correction on myocardial tracer distribution.

UNLABELLED: This study evaluates the effect of attenuation correction on regional myocardial tracer distributions defined by 201TI cardiac perfusion SPECT images obtained from healthy volunteers and patients with coronary heart disease. METHODS: A three-detector SPECT system equipped with an 241Am line source and a fanbeam collimator was used for simultaneous transmission/emission (201TI) tomography on 40 patients and 10 normal volunteers. Uncorrected emission images were reconstructed using filtered backprojection (FBP), whereas the attenuation corrected images were iteratively reconstructed with a regularized, least-squares algorithm utilizing the attenuation map computed from the transmission data. Both sets of images were reoriented into short-axis and vertical long-axis slices. Circumferential profile analysis was applied to both datasets of short-axis slices. RESULTS: The normal volunteers demonstrated improved homogeneity in tracer distribution. For a basal short-axis slice, the lateral-to-posterior activity ratio improved from 1.17 +/- 0.12 for FBP to 1.01 +/- 0.07. Basal attenuation appeared properly compensated as the peak basal-to-apical slice activity gradient along the posterior-inferior wall changed from 1.15 +/- 0.12 for FBP to 1.01 +/- 0.09. The apex of the attenuation corrected images showed a significant decrease in activity relative to the base which appeared consistent with anatomic wall thinning. For the inferior and basal septal regions, the defect severity was slightly less in the attenuation corrected images, but the defects were more sharply defined compared to the FBP image defects. CONCLUSION: These results indicate that attenuation correction is clinically feasible and accurately corrects for photon attenuation. Clinical validation, however, is necessary to define the diagnostic benefits.

Coronary Disease↗
PubMed1995

Adrenocortical function in neonatal and weanling beagle pups.

Adrenocortical function was assessed in 27 Beagle pups at 2, 4, 6, 8, 10, and 12 weeks of age by determination of plasma sodium, potassium, and chloride concentrations; serum aldosterone and cortisol concentrations; and plasma ACTH concentrations. Serum cortisol concentration was measured before and 1 and 2 hours after IM administration of 2.2 IU of ACTH/kg of body weight. Serum progesterone concentration also was determined for all pups at 2, 4, and 6 weeks of age. Mean baseline cortisol concentration was lower for pups 8 weeks old or younger than for mature dogs. Nevertheless, mean serum ACTH-stimulated cortisol concentration in dogs of all age groups increased into the adult reference range after administration of ACTH. For pups 4 weeks old or younger, increase in cortisol concentration was maximal at 2 hours after ACTH administration. However, in pups between 6 and 12 weeks of age, the increase in cortisol concentration was maximal 1 hour after ACTH administration in about a third of the pups, whereas the remaining pups had peak values at 2 hours. Mean plasma sodium, potassium, and chloride concentrations for each age group were within the reference ranges established for mature dogs, with the exception of lower mean plasma sodium and chloride concentrations in pups 4 weeks old or younger. Mean serum aldosterone concentration in pups of each age group was substantially higher than the range of aldosterone concentrations for clinically normal mature dogs. Median progesterone concentration was uniformly less than 0.2 ng/ml for all pups 6 weeks old or younger.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1994

Synthesis and evaluation of a new class of technetium-99m monocationic radiotracers from dithienyldiazalkanes.

Monocationic 99mTc complexes, [99mTcO2 (THEN)]+ and [99mTcO2(THPN)]+ derived from a new class of N2S2 chelators diethienyldiazalkanes, namely 1,6-di(2-thienyl)-2,5-diazahexane (THEN) and 1,7-di- (2-thienyl)-4,4-dimethyl-2,6-diazaheptane (THPN), have been synthesized using Sn(II) tartrate reduction of [99mTc]pertechnetate at pH 9 and extraction of the complexes as ion pairs with trifluoromethane sulfonate anion (CF3SO3-) in high radiochemical yield (approximately 90%). Radiochemical analysis of the 99mTc complexes using chromatography (Whatman Cellulose CEL300 DEAE anion exchange strip, MEK) and paper chromatography (Whatman I, acetone) revealed high radiochemical purity (> 90%). High octanol-saline partition coefficients (> 37) of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ indicated a lipophilic nature of the complexes. Relative stability of the 99mTc complex was high as measured by DTPA challenge studies. Biodistribution of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ in rats at 15 min post-injection showed heart-to-blood activity ratios of 0.26 and 0.46, respectively, with rapid blood clearance. Further studies involving the variation of substituents on the basic core structure of this new class of 99mTc complexes may provide radiotracers suitable for myocardial imaging.

Animals↗
PubMed1994

An audit of dermatology in a paediatric accident and emergency department.

Two studies were undertaken of patients with dermatological disorders who attended the Accident and Emergency (A&E) Department of the Royal Belfast Hospital for Sick Children during 1990-1991. The aims were to review diagnostic accuracy and assess the benefits of an open-access consultant dermatology clinic. A retrospective survey of 14,340 new attendances at the A&E department over a 7-month period found that 540 of these (4%) had a primary dermatological disorder. In 26% no diagnosis had been made although only 10% were referred for a specialist opinion. A 2-month prospective study of patients who attended the department and were referred to a consultant dermatology open-access clinic revealed overall diagnostic accuracy of 66% (+/- 2 SEM). Individual rates of diagnostic concordance between junior doctor and consultant were 59% for skin infections and 77% for papulosquamous disorders. The open-access clinic allowed prompt referral for correct diagnosis and initiation of appropriate management.

Adolescent↗
PubMed1993

Prevalence of mycoplasmal and ureaplasmal recovery from tracheobronchial lavages and of mycoplasmal recovery from pharyngeal swab specimens in cats with or without pulmonary disease.

The prevalence of mycoplasmal and ureaplasmal recovery from tracheobronchial lavage specimens and prevalence of mycoplasmal recovery from pharyngeal swab specimens from cats with (28) or without (18) pulmonary disease were determined. Mycoplasmas were recovered from tracheobronchial lavage specimens in 21% of cats with pulmonary disease, but in no cats without pulmonary disease; this difference is significant (P = 0.04). Mycoplasmal recovery from tracheobronchial lavage specimens was not significantly associated with concurrent Pasteurella spp isolation, septic inflammation, or bronchitis. Ureaplasmas were only isolated from a tracheobronchial lavage specimen in 1 cat with pulmonary disease and in no cats without pulmonary disease. Similar mycoplasmal recovery rates were found for pharyngeal swab specimens from cats with (39%) or without (35%) pulmonary disease. Seemingly, mycoplasmas are part of the normal pharyngeal flora in approximately a third of the feline population, but mycoplasmas are not normal inhabitants of the lower respiratory tract in cats. It is unknown whether mycoplasmas isolated from tracheobronchial lavage specimens in cats with pulmonary disease are primary pathogens or opportunistic invaders. Seemingly, ureaplasmas are seldom associated with pulmonary disease in cats, and are not normal inhabitants of the trachea and bronchi of cats.

Age Factors↗