Pulmonary embolism: computer-aided detection at multidetector row spiral computed tomography

BACKGROUND: We aimed to evaluate the feasibility and performance of a computer-aided detection (CAD) tool for automated detection of segmental and subsegmental pulmonary emboli. METHODS: A CAD tool (ImageChecker CT, R2 Technology, Inc) for automated detection of pulmonary emboli was evaluated on multidetector-row CT studies of varying diagnostic quality in 23 patients (13 female, mean age 52 y) with pulmonary embolism (PE) and of 13 patients (all female, mean age 49 y) without PE. A collimation of 16 x 1 mm and a reconstructed section width of 1.25 mm had been used in each patient. The performance of the CAD tool for the detection of emboli in the segmental and subsegmental pulmonary arterial tree was assessed. Consensus reading of the same studies by 2 radiologists, with a third for adjudication, for the identification of segmental and subsegmental pulmonary emboli was used as the standard of reference. RESULTS: Consensus reading revealed 130 segmental pulmonary emboli and 107 subsegmental pulmonary emboli in the 23 patients with PE. All 23 patients with PE were correctly identified as having PE by the CAD system. In a vessel-by-vessel analysis, the sensitivity of the CAD algorithm was 92% (119/130) for the detection of segmental pulmonary emboli and 90% (92/107) for subsegmental pulmonary emboli. The overall specificity, positive predictive value (95% confidence interval) and negative predictive value (95% confidence interval) of the algorithm were 89.9%, 63.2% (57.9%-68.2%) and 97.7% (96.7%-98.4%), respectively. The average false positive rate of the CAD algorithm was 4.8 (range 1 to 9) false positive detection marks per case. CONCLUSION: CAD of segmental and subsegmental pulmonary emboli based on 1-mm multidetector-row CT studies is feasible. Application of CAD tools may improve the diagnostic accuracy and decrease the interpretation time of computed tomographic angiography for the detection of pulmonary emboli in the peripheral arterial tree and further enhance the acceptance of this test as the first line diagnostic modality for suspected PE.     

The clinical significance of the spectrum of interactions of CAP+1 (A-->C), a silent beta-globin gene mutation, with other beta-thalassemia mutations and globin gene modifiers in north Indians

OBJECTIVES: To assess the clinical significance of the interactions of CAP+1 (A-->C), a silent beta-globin gene mutation, with other beta-thalassemia mutations and globin gene modifiers in north Indians. METHODS: The clinical phenotypes associated with compound heterozygosity for the CAP+1 (A-->C) mutation with other beta-thalassemia mutations, together with the potential effect of the genetic modifiers alpha-thalassemia and the Xmn-1(G)gamma C-->T polymorphism were studied in 30 patients. The frequency of the CAP+1 (A-->C) polymorphism was determined and an analysis of the red cell indices, HbA(2) levels, iron status, and alpha-globin genes was carried out in 35 heterozygotes. RESULTS: Based on an analysis of 1075 beta-thalassemia alleles the CAP+1 (A-->C) mutation constituted 3.2% of north Indians. There was a wide spectrum of phenotypic severity in compound heterozygotes; 18 of 30 were transfusion dependent. There was a very high frequency of the -/- genotype of the Xmn-1(G)gamma polymorphism in compound heterozygotes. Analysis of 35 heterozygotes indicated that approximately half were hematologically normal and therefore genuine 'silent' carriers. CONCLUSIONS: Compound heterozygotes for CAP+1 (A-->C) and other severe beta-thalassemia alleles are phenotypically severe enough to necessitate appropriate therapy and counseling. The unexpected severity of these interactions may be due, in part, to the high frequency of beta-thalassemia alleles associated with the Xmn-1(G)gamma- allele in Indian populations. It is concluded that the CAP+1 (A-->C) mutation can pose serious difficulties in screening and counseling programs in populations in which it occurs at a significant frequency.     

Low levels of plasma soluble complement receptor type 1 in patients receiving thrombolytic therapy for acute myocardial infarction

Background Administration of recombinant soluble CR1 (sCR1) has been shown to attenuate complement mediated myocardial injury in animal models of acute MI. The plasma level of sCR1 in humans with acute MI is not known. We determined the levels of the complement regulatory protein, complement receptor type-1 (CR1) in plasma and its expression on the surface of leukocytes of patients receiving thrombolysis for acute myocardial infarction (AMI). Methods Plasma sCR1 was measured by a sandwich ELISA. The levels in patients with AMI were compared with those in normal controls. Leukocyte surface expression of CR1 was measured by flowcytometry. We correlated these parameters with clinical outcome and left ventricular ejection fraction. Results Patients had very low plasma sCR1 levels. Mean plasma sCR1 levels were significantly less than in controls (6 ± 3.6 ng/mL vs. 44.6 ± 12.2 ng/mL, P < 0.00001). Patients who had an adverse in-hospital outcome had significantly lower sCR1 levels when compared to those who had an uneventful course (3.8 ± 2.0 ng/mL and 7.1 ± 3.8 ng/mL respectively, P = 0.01). The low plasma sCR1 was despite significantly greater lymphocyte and monocyte surface CR1 (which is a potential source of plasma sCR1). Conclusion Plasma sCR1 levels are reduced in patients receiving thrombolysis for AMI. Replenishing plasma sCR1 might limit complement-mediated injury in this setting.     

Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions

Background: Insulin resistance plays an important role in the pathogenesis of NAFLD. Pharmacological treatment of patients with NAFLD is still evolving. Insulin sensitizing drugs like metformin may be effective in these patients. Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases (ALT) after 6 months of lifestyle interventions and UDCA were treated with metformin 500mg tid for 6 months. Insulin resistance was determined by HOMA-IR. Liver function tests were done monthly and patients were defined having no response, partial response or complete biochemical response depending on the change in ALT. Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions (disease controls). Results: Thirteen (52%) patients had class III (n = 5) or class IV (n = 8) disease amounting to histological NASH. Of these 13 patients none had severe inflammation and none had stage 4 fibrosis (cirrhosis). All 25 patients with NAFLD had insulin resistance in comparison to healthy controls. In comparison to disease controls (127.5 ± 41.8 vs. 118 ± 21.6 p = NS), all patients treated with metformin had partial biochemical response (mean ALT 122.2 ± 26.8 vs 74.3 ± 4.2 p < 0.01) and 14 (56%) of them achieved complete normalization of ALT. Conclusions: Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions and UDCA.     

Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India

Most studies of cognitive functioning in human immunodeficiency virus type 1 (HIV-1)-seropositive (HIV-1+) subjects have been done in the United States and Europe, where clade B infections predominate. However, in other parts of the world such as South India, where clade C HIV is most common, the prevalence of HIV-1 is increasing. Standardized neuropsychological tests were used to assess cognitive functioning in a sample of 119 adults infected with clade C HIV-1 who were not on antiretroviral medications. The subjects did not have neurological or psychiatric illness and were functioning adequately. Neuropsychological test performance was compared with gender-, age-, and education-matched normative data derived from a sample of 540 healthy volunteers and a matched cohort of 126 healthy, HIV-1-seronegative individuals. Among the seropositive subjects, 60.5% had mild to moderate cognitive deficits characterized by deficits in the domains of fluency, working memory, and learning and memory. None of the subjects had severe cognitive deficits. The HIV-1+ sample was classified into groups according to the level of immune suppression as defined by CD4 count (<200, 201–499, and >500 cells/mm³) and viral load (<5000, 5001–30,000, 30,001–99,999, 100,000–1,000,000, and >1,000,001 copies). Although the most immunosuppressed group (CD4 count <200 cells/mm³ or viral load >1,000,001 copies) was small, their rate of impairment in visual working memory was greater when compared to groups with better immune functioning. Mild to moderate cognitive deficits can be identified on standardized neuropsychological tests in clade C-infected HIV-1+ adults who do not have any clinically identifiable functional impairment. The prevalence of cognitive deficits is similar to that reported in antiretroviral treatment-naïve individuals infected with clade B virus in the western world.     

Chordomas of the craniospinal axis: multimodality surgical, radiation and medical management strategies

Chordomas are neoplasms of the primitive notochord remnants and are characterized by slow growth kinetics, locally aggressive behavior and resistance to conventional therapeutic options. They are found primarily in the skull base or the sacral region, although they can occur anywhere in the craniospinal axis. If an oncologic surgical resection can be performed safely, patients derive the maximal benefit. Adjuvant radiotherapy has a proven benefit in both progression-free and overall survival. Chemotherapy plays a limited role and currently remains an option at tumor recurrence, although increasing knowledge of the molecular biology of chordomas may lead to targeted therapeutic strategies. In this review, the current multimodality treatment strategy for chordomas will be discussed and future directions will be highlighted.     

The accuracy of 1- and 3-mm slices in coronary calcium scoring using multi-slice CT in vitro and in vivo

The accuracy of coronary calcium scoring using 16-row MSCT comparing 1- and 3-mm slices was assessed. A thorax phantom with calcium cylinder inserts was scanned applying a non-enhanced retrospectively ECG-gated examination protocol: collimation 12×0.75 mm; 120 kV; 133 mAs_eff. Thirty-eight patients were examined using the same scan protocol. Image reconstruction was performed with an effective slice thickness of 3 and 1 mm. The volume score, calcium mass and Agatston score were determined. Image noise was measured in both studies. The volume score and calcium mass varied less than the Agatston score. The overall measured calcium mass compared to the actual calcium mass revealed a relative difference of +2.0% for 1-mm slices and −1.2% for 3-mm slices. Due to increased image noise in thinner slices in the patient study (26.1 HU), overall calcium scoring with a scoring threshold of 130 HU was not feasible. Interlesion comparison showed significantly higher scoring results for thinner slices (all P<0.001). A similar accuracy comparing calcium scoring results of 1- and 3-mm slices was shown in the phantom study; therefore, the potentially necessary increase of the patient's dose in order to achieve assessable 1-mm slices with an acceptable image-to-noise-ratio appears not to be justified. The study was supported by a “START” grant from the University Hospital of Aachen, Germany.     

Functional analysis of novel KCNQ2 mutations found in patients with Benign Familial Neonatal Convulsions

Benign Familial Neonatal Convulsions (BFNC) are a rare epilepsy disorder with an autosomal-dominant inheritance. It is linked to mutations in the potassium channel genes KCNQ2 and KCNQ3. These encode for Kv7.2 and Kv7.3 potassium ion channels, which produce an M-current that regulates the potential firing action in neurons through modulation of the membrane potential. We report on the biophysical and biochemical properties of V589X, T359K and P410fs12X mutant-KCNQ2 ion channels that were detected in three BFNC families. Mutant KCNQ2 cDNAs were co-expressed with WT-KCNQ2 and KCNQ3 cDNAs in HEK293 cells to mimic heterozygous expression of the KCNQ2 mutations in BFNC patients. The resulting potassium currents were measured using patch-clamp techniques and showed an approximately 75% reduction in current and a depolarized shift in the voltage dependence of activation. Furthermore, the time-constant of activation of M-currents in cells expressing T359K and P410fs12X was slower compared to cells expressing only wild-type proteins. Immunofluorescent labeling of HEK293 cells stably expressing GFP-tagged KCNQ2-WT or mutant α-subunits indicated cell surface expression of WT, V589X and T359K mutants, suggesting a loss-of-function, while P410fs12X was predominantly retained in the ER and sub-cellular compartments outside the ER suggesting an effectively haplo-insufficient effect.     

(1)H and (31)P NMR studies indicate reduced bile constituents in patients with biliary obstruction and infection

Patients with extrahepatic biliary obstruction present with impairment of the normal bile flow, with jaundice and cholangitis as common complications. (1)H and (31)P NMR quantitative analysis of bile specimens from patients with extrahepatic biliary obstruction (n = 80) (with/without jaundice and cholangitis separately and together) was carried out for the chief biliary constituents to determine the relationship between biliary constituents and jaundice (serum bilirubin concentration >or=1.0 mg/dL) and cholangitis (total leucocyte count >11,000 cells/mm(3) and/or fever >38.5 degrees C with/without bile culture positivity). Compared with controls (patients without jaundice and cholangitis), median indices of the chief biliary constituents (total bile acids, cholesterol, phosphatidylcholine and inorganic phosphate) were significantly suppressed in patients with cholangitis and/or jaundice. Quantities of total bile acids, cholesterol and phosphatidylcholine correlated negatively with the quantity of bilirubin and with cholangitis, i.e. total leucocyte count. Suppression of biliary constituents correlated significantly with the severity of jaundice and cholangitis. The decrease in biliary constituents in the presence of jaundice and cholangitis is possibly the result of downregulation of the function of transporters located at the canalicular side of hepatocytes, leading to their suppressed indices in bile. This information may have implications in the examination of bile for clinical studies.