Influence of anatomic correction for transposition of the great arteries on myocardial perfusion: Radionuclide imaging with technetium-99m 2-methoxy isobutyl isonitrile

AbstractObjectives. We sought to determine the incidence of late perfusion defects attributable to coronary artery mobilization in patients undergoing anatomic correction for complete transposition of the great arteries.Background. Anatomic correction (arterial switch procedure) is currently the surgical treatment of choice for complete transposition. From its conception, there has been concern about the impact on myocardial perfusion of the coronary artery mobilization and reimplantation involved in the correction. Previous studies have demonstrated myocardial perfusion defects in patients after correction, although a causal relation between coronary mobilization, and perfusion abnormality has not been established.Methods. In a case-comparison study designed to test this hypothesis, 29 children underwent imaging with technetium-99m 2-methoxy isobutyl isonitrile (technetium-99m mibi). Ten had undergone anatomic correction (arterial switch group; interval from operation 6.9 ± 1.42 years [range 4.9 to 9.1]); 9 had required noncoronary open heart surgery for other cardiac lesions (postbypass group; interval from operation 5.6 ± 3.6 years [range 1.0 to 13.25]); and 10 had had no surgical procedure (control group). The latter group comprised children with atrial or ventricular septal defects who required a radionuclide study for shunt calculation. Planar studies were performed in all 29 children, and additional tomographic acquisition was achieved in 25. To assess reversibility of perfusion defects both an exercise and a rest planar study were performed in the arterial switch group.Results. Perfusion abnormalities were observed in seven of the nine children in the postbypass group and in all 10 children in the arterial switch group. The frequency of perfusion defects in these two groups was similar, with at least 25% of the tomographic segments reported being abnormal. The control group had significantly fewer defects than the other two groups (p = 0.02), with only 8% of the tomographic segments judged to be abnormal. In all except one patient in the arterial switch group, the segments reported as abnormal on the planar exercise study were either abnormal or equivocal on the rest study, indicating a fixed abnormality.Conclusions. Although the precise etiology of these perfusion abnormalities cannot be defined from this study, these data suggest that their origin is related more to the insult of open heart surgery itself than to the coronary manipulation involved in the arterial switch procedure. The functional importance requires further study

Double-outlet right ventricle: Morphologic demonstration using nuclear magnetic resonance imaging

Sixteen patients with double-outlet right ventricle, aged 1 week to 29 years (median 5 months), were studied with a 1.5 tesla nuclear magnetic resonance (NMR) imaging scanner. Two-dimensional echocardiography was performed in all patients. Thirteen patients underwent angiography, including nine who underwent subsequent surgical correction. Three patients underwent postmortem examination.Small children and infants were scanned inside a 32 cm diameter proton head coil. Multiple 5 mm thick sections separated by 0.5 mm and gated to the patient's electrocardiogram were acquired with a spin-echo sequence and an echo time of 30 ms. A combination of standard and oblique imaging planes was used. Imaging times were <90 min. The NMR images were technically unsuitable in one patient because of excessive motion artifact.In the remaining patients, the diagnosis of double outlet right ventricle was confirmed and correlated with surgical and postmortern findings. The NMR images were particularly valuable in demonstrating the interrelations between the great arteries and the anatomy of the outlet septum and the spatial relations between the ventricular septal defect and the great arteries. Although the atrioventricular (AV) valves were not consistently demonstrated, NMR imaging in two patients identified abnormalities of the mitral valve that were not seen with two-dimensional echocardiography. In one patient who had a superoinferior arrangement of the ventricles, NMR imaging was the most useful imaging technique for demonstrating the anatomy.In patients with double-outlet right ventricle, NMR imaging can provide clinically relevant and accurate morphologic information that may contribute to future improvement in patient management

First shark from the late Devonian (Frasnian) gogo formation, Western Australia sheds new light on the development of tessellated calcified cartilage

Background: Living gnathostomes (jawed vertebrates) comprise two divisions, Chondrichthyes (cartilaginous fishes, including euchondrichthyans with prismatic calcified cartilage, and extinct stem chondrichthyans) and Osteichthyes (bony fishes including tetrapods). Most of the early chondrichthyan (‘shark’) record is based upon isolated teeth, spines, and scales, with the oldest articulated sharks that exhibit major diagnostic characters of the group—prismatic calcified cartilage and pelvic claspers in males—being from the latest Devonian, c. 360 Mya. This paucity of information about early chondrichthyan anatomy is mainly due to their lack of endoskeletal bone and consequent low preservation potential. Methodology/Principal Findings: Here we present new data from the first well-preserved chondrichthyan fossil from the early Late Devonian (ca. 380–384 Mya) Gogo Formation Lägerstatte of Western Australia. The specimen is the first Devonian shark body fossil to be acid-prepared, revealing the endoskeletal elements as three-dimensional undistorted units: Meckel’s cartilages, nasal, ceratohyal, basibranchial and possible epibranchial cartilages, plus left and right scapulocoracoids, as well as teeth and scales. This unique specimen is assigned to Gogoselachus lynnbeazleyae n. gen. n. sp.Conclusions/Significance: The Meckel’s cartilages show a jaw articulation surface dominated by an expansive cotylus, and a small mandibular knob, an unusual condition for chondrichthyans. The scapulocoracoid of the new specimen shows evidence of two pectoral fin basal articulation facets, differing from the standard condition for early gnathostomes which have either one or three articulations. The tooth structure is intermediate between the ‘primitive’ ctenacanthiform and symmoriiform condition, and more derived forms with a euselachian-type base. Of special interest is the highly distinctive type of calcified cartilage forming the endoskeleton, comprising multiple layers of nonprismatic subpolygonal tesserae separated by a cellular matrix, interpreted as a transitional step toward the tessellated prismatic calcified cartilage that is recognized as the main diagnostic character of the chondrichthyans

Gemcitabine with a specific conformal 3D 5FU radiochemotherapy technique is safe and effective in the definitive management of locally advanced pancreatic cancer

The aim of this phase II study was to assess the feasibility and efficacy of a specific three-dimensional conformal radiotherapy technique with concurrent continuous infusion of 5-fluorouracil (CI 5FU) sandwiched between gemcitabine chemotherapy in patients with locally advanced pancreatic cancer. Patients with inoperable cancer in the pancreatic head or body without metastases were given gemcitabine at 1000 mg m−2 weekly for 3 weeks followed by a 1-week rest and a 6-week period of radiotherapy and concurrent CI 5FU (200 mg m−2 day−1). The defined target volume was treated to 54 Gy in 30 daily fractions of 1.8 Gy. After 4 weeks' rest, gemcitabine treatment was re-initiated for three cycles (days 1, 8, 15, q28). Forty-one patients were enrolled. At the end of radiotherapy, one patient (2.4%) had a complete response and four patients (9.6%) had a partial response; at the end of treatment, three patients (7.3%) had a complete response and two patients (4.9%) had a partial response. Median survival time was 11.7 months, median time to progression was 7.1 months, and median time to failure of local control was 11.9 months. The 1- and 2-year survival rates were 46.3 and 9.8%, respectively. Treatment-related grade 3 and 4 toxicities were reported by 16 (39.0%) and four (9.8%) patients, respectively. Sixteen out of 41 patients did not complete the planned treatment and nine due to disease progression. This approach to treatment of locally advanced pancreatic cancer is safe and promising, with good local control for a substantial proportion of patients, and merits testing in a randomised trial

Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems

Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications

Cost-effectiveness of preoperative positron emission tomography in ischemic heart disease.

BACKGROUND: Revascularization of patients with ischemic heart disease and poor left ventricular function for surgical procedures is expensive and carries considerable risks, but may improve survival for patients with hibernating myocardium. Positron emission tomography can detect hibernating myocardium, and may be cost-effective if used to select patients for operation. METHODS: An economic model was developed to compare the cost-effectiveness of three management strategies: (1) coronary artery bypass grafting for all patients; (2) using positron emission tomography to select candidates for coronary artery bypass grafting, those without hibernation remaining on medical therapy; and (3) medical therapy for all patients. The model used data from our hospital and the published literature. A sensitivity analysis was also undertaken. RESULTS: Positron emission tomography was cost-effective in selecting patients for operation. In a hypothetical population of 1,000 patients, using positron emission tomography saved marginally more life-years and cost approximately Pound Sterling 3 million less. Using positron emission tomography before coronary artery bypass grafting instead of all patients receiving medical treatment saved lives but was more expensive. The incremental cost per life-year saved was Pound Sterling 77,000. The sensitivity analysis showed that the prevalence of hibernation and the survival rate of patients refused revascularization on the basis of the positron emission tomography scan were the areas most likely to influence cost-effectiveness. CONCLUSIONS: Positron emission tomography may be cost-effective to select patients with poor left ventricular function for coronary artery bypass grafting

Evaluation of the limits of visual detection of image misregistration in a brain fluorine-18 fluorodeoxyglucose PET MRI study

In routine clinical work, registration accuracy is assessed by visual inspection. However, the accuracy of visual assessment of registration has not been evaluated. This study establishes the limits of visual detection of misregistration in a registered brain fluorine-18 fluorodeoxyglucose positron emission tomography to magnetic resonance image volume. The ldquobestrdquo registered image volume was obtained by automatic registration using mutual information optimization. Translational movements by 1 mm, 2 mm, 3 mm and 4 mm, and rotational movements by 1°, 2°, 3° and 4° in the positive and negative directions in the x- (lateral), y- (anterior-posterior) and z- (axial) axes were introduced to this standard. These 48 images plus six ldquobestrdquo registered images were presented in random sequence to five observers for visual categorization of registration accuracy. No observer detected a definite misregistration in the ldquobestrdquo registered image. Evaluation for inter-observer variation using observer pairings showed a high percentage of agreement in assigned categories for both translational and rotational misregistrations. Assessment of the limits of detection of misregistration showed that a 2-mm translational misregistration was detectable by all observers in the x- and y-axes and 3-mm translational misregistration in the z-axis. With rotational misregistrations, rotation around the z-axis was detectable by all at 2° rotation whereas rotation around the y-axis was detected at 3–4°. Rotation around the x-axis was not symmetric with a positive rotation being identified at 2° whereas negative rotation was detected by all only at 4°. Therefore, visual analysis appears to be a sensitive and practical means to assess image misregistration accuracy. The awareness of the limits of visual detection of misregistration will lead to increase care when evaluating registration quality in both research and clinical settings

Positron emission tomography: clinical practice

This book provides a contemporary reference to the science, technology and clinical applications of PET and PET/CT. The opening chapters summarize the scientific aspects of PET and PET/CT including physics, instrumentation, radiation dosimetry and radiation protection. A chapter on normal variants in FDG PET imaging serves as an introduction to the clinical chapters, which cover oncology applications and have been updated to include the impact of FDG PET/CT imaging in oncology. The book concludes with chapters on the use of PET and PET/CT in cardiology and neurology and PET imaging of infecti