Human placental glutathione transport mechanism

The placental transport mechanism of glutathione (GSH) was investigated using microvillous membrane vesicles prepared from human term placenta. Using (3H-glycine)-labeled-GSH, it was clarified that GSH in the extravesicular compartment of placental microvillous membranes was rapidly degraded by gamma-GTP (gamma-glutamyltranspeptidase) and resulting amino acid, and 3H-labeled-glycine was actively transported via a sodium cotransport system. AT-125 treated microvillous membrane vesicles almost entirely lost its gamma-GTP activity, and showed intact GSH transport. Using AT-125 treated microvillous membrane vesicles, it was revealed that GSH was transported across the microvillous membrane as an anion via a membrane potential-dependent mechanism. These results indicated that gamma-GTP which existed in microvillous membrane played a role in GSH metabolism and that intracellular GSH was translocated out of the syncythiotrophoblast cell into the maternal blood space via a specific carrier in microvillous membrane because the GSH concentration was higher in intracellular than extracellular and extracellular membrane potential was positively charged.     

Supraventricular bigeminy originating from the mitral annulus: What is the mechanism?

We present a case of a 67‐year‐old female with a previous history of pulmonary vein isolation for paroxysmal atrial fibrillation who presented with supraventricular bigeminy with a constant coupling interval. The supraventricular bigeminy originated from the anterior mitral annulus with initial mapping suggestive of a focal mechanism. However detailed mapping using an ultrahigh resolution mapping system (with the manual shifting of the annotation window) revealed very low amplitude potentials connecting the previous sinus beat with continuous activation along the mitral annulus. Our observations were indicative of a re‐entry mechanism underlying the supraventricular bigeminy.     

QRS characteristics fail to reliably identify ventricular tachycardias that require epicardial ablation in ischemic heart disease

Criteria for Epicardial Origin in Ischemic VT. Objectives: We tested proposed algorithms for idiopathic and nonischemic tachycardias for their ability to identify epicardial LV‐VT origins. Backgroud: Several ECG features have been reported to identify epicardial origins for left ventricular tachycardias (LV‐VTs) in the absence of myocardial infarction. Only limited data exist in postinfarction patients. Methods: The QRS features of 24 VTs that were ablated from the epicardium and 39 left ventricular VTs ablated from the endocardium were retrospectively analyzed for various 12‐lead ECG features previously reported. Results: No ECG feature consistently predicted an epicardial LV‐VT origin in infarct‐related tachycardias, with epicardial VTs showing slightly longer QRS durations (189 ± 32 ms in epicardial vs 179 ± 37 ms in endocardial, P = 0.28). Pseudo‐delta duration was 38 ± 27 versus 47 ± 27 ms (P = 0.2), intrinsicoid deflection time 93 ± 35 versus 86 ± 32 ms (P = 0.4), shortest RS 97 ± 38 versus 99 ± 32 ms (P = 0.77), and median deflection index 0.82 ± 0.25 versus 0.87 ± 0.22 (P = 0.43). The finding of a Q wave in lead I and the absence of a Q wave in the inferior leads failed to predict an epicardial origin in superior LV‐VT sites. Q waves in any inferior lead and aVR/aVL‐ratio<1 were not specific for an epicardial origin in inferior sites (all P = ns). Furthermore, all inferior LV‐VTs showed a Q wave in the inferior leads which correlated with pre‐existing Q‐waves in sinus rhythm (P = 0.045). Conclusion : Proposed 12‐lead ECG features for differentiation of epicardial versus endocardial sites for nonischemic LV‐VTs do not reliably identify VTs that require ablation from the epicardium. Endocardial mapping should be the first approach to catheter ablation for VTs in patients with ischemic heart disease. (J Cardiovasc Electrophysiol, Vol. 23, pp. 188‐193, February 2012)     

Early positive biomarker in relation to myocardial necrosis and impaired fatty acid metabolism in patients presenting with acute chest pain at an emergency room.

BACKGROUND: Measurement of circulating biomarkers has enabled early diagnosis and risk assessment of acute coronary syndrome. This study sought diagnostic values of the first single-point data of biomarkers obtained soon after patient arrival by comparing with scintigraphically quantified myocardial injury in patients presenting with acute chest pain at an emergency room. METHODS AND RESULTS: Serial blood samples were taken soon after arrival in an emergency department in 74 patients with suspected acute coronary syndrome to quantify blood levels of troponin-T (TnT), heart-type fatty acid-binding protein (H-FABP), myocardial-bound creatine kinase (CK-MB), and myoglobin. Myocardial perfusion and metabolic defects were scintigraphically quantified. The first single-point data had high positive predictive values for detecting the defects (80-100%) but low negative predictive values (15-41%). CK-MB and TnT had higher specificities (73-100%) but significantly lower positive rates (22-27%) than the others (61-68%), resulting in greater sensitivities of H-FABP and myoglobin (75-80%) than those of CK-MB and TnT (29-35%). Among biomarkers, TnT peak concentrations most closely correlated with scintigraphic abnormalities. CONCLUSION: H-FABP can contribute to early detection of myocardial injury and TnT is most likely to correlate with injured myocardial mass. The differential features of biomarkers are complementary in patients with acute chest pain presenting at an emergency room.     

Validation of quantitative gated single photon emission computed tomography and an automated scoring system for the assessment of regional left ventricular systolic function

Despite its ability to quantify regional perfusion and function, there is no established method for quantification of regional perfusion and function by myocardial gated single photon emission computed tomography (SPECT). The aim of this study was to establish a quantitative index for regional perfusion and systolic function assessment using gated SPECT. Myocardial SPECT was performed at rest using (99m)Tc sestamibi with 8-frame gating in 62 consecutive patients. In addition to computation of left ventricular ejection fraction (LVEF), a new computerized method for quantifying, displaying and automatically grading regional data was developed. Regional function was quantified as wall motion, regional EF, and imaged based, count based, and normalized per cent wall thickenings (%WTs). Regional perfusion was assessed as a relative per cent peak count. Data were displayed on a 25-segmented polar map and automatically graded with a 5-point scale, and then summed scores were calculated. These quantitative parameters were compared to data from radionuclide ventriculography (RNV) and contrast left ventriculography. Gated SPECT had high reproducibilities for calculating global and regional ejection fractions and %WT indices (r=0.811-0.984, P<0.0001), but measurement of wall motion was less reproducible (r=0.555, SEE=7.9, P<0.011). LVEF estimated by gated SPECT and summed perfusion scores correlated closely (P<0.0001) with angiographic LVEF. Among the summed function indices that correlated closely with LVEF, normalized %WT had the closest correlations with LVEF estimated by RNV (r=0.657, P<0.0001) and by gated SPECT (r=0.778, P<0.0001). Assessment by visual reviewing of cine-mode playback or by normalized %WT had greater overall sensitivity, specificity, and positive and negative predictive values for detecting impaired regional function among the functional parameters: 71%, 79%, 63% and 84% for cine format analysis, and 78%, 73%, 59% and 87% for normalized %WT, respectively. Thus, besides LVEF, quantitative gated SPECT can provide reproducible and reliable quantitative data on regional perfusion and function. Automated summed scores obtained by gated SPECT can reflect integrated abnormalities of regional perfusion and function of the left ventricle. Both visual analyses by cine-mode display and a functional map of normalized wall thickening have greater diagnostic values for detecting regional function deficit related to coronary artery disease.     

Quantitative assessment of right ventricular structural abnormalities by right ventricular polar mapping of single photon emission computed tomogram

The identification of right ventricular (RV) abnormalities is clinically important in the evaluation of arrhythmogenic substrates in right ventricular-originated ventricular tachycardia (RVT). The purpose of this study was to determine the diagnostic benefit of quantitative analysis in RV single photon emission computed tomography (SPECT) imaging with (99m)Tc-tetrofosmin/sestamibi in patients with RVT. Thirty patients with RVT (15 with idiopathic RVT and 15 with arrhythmogenic right ventricular cardiomyopathy (ARVC)) were compared with 27 control subjects (including 11 with right bundle branch block) with regard to the semiquantitative RV uptake score in each of six segments and the quantitative RV extent score in polar coordinate map displays by SPECT imaging. The RV total score and RV extent score were compared with the RV global function. Perfusion abnormalities were more frequently detected (P = 0.0001) in the ARVC group (59/90, 65.6%) than in the idiopathic RVT group (4/90, 4.4%) or controls (1/162, 0.6%). The RV extent score in the ARVC group (53.0 +/- 24.8) was significantly higher than that in the idiopathic RVT group (8.4 +/- 10.1) or controls (1.2 +/- 4.9). The RV extent score correlated well with the regional RV perfusion score (P < 0.0001) and with the RV ejection fraction (P < 0.0001). Non-invasive RV perfusion mapping using a (99m)Tc-labelled tracer is useful for the quantitative evaluation of RV substrates in patients with ARVC.     

Bone Marrow Transplantation for Hematologicai Diseases in Hokkaido--June 1985 to December 1991

Bone marrow transplantation (BMT) was started in Hokkaido in1985. In the present report we have reviewed the clinical outcomeof patients treated with BMT for hematologicai diseases in Hokkaido.Fifty-eight allogeneic and 19 autologous transplants were registeredby December 1991. The underlying diseases consisted of 47 leukemias,14 lymphomas, 10 aplastic anemias and six myelodysplastic syndromes.Among the allogeneic BMT cases, 55 were human leuhocyte antigen(HLA) identical and three were mismatched. Among the autologousBMT patiets, two recieved their marrow purged with 4-hydroperoxycyclophosphamideand five, with monoclonal antibodies and complements. The conditioningregimens used for malignancies were chiefly cyclophosphamide(CY) plus total body irradiation, or busulfan plus CY. In manycases, cytokines were used for rapid recovery of decreased leukocytes.Engraftment was observed in 50 out of 52 evaluated allogeneicand 18 out of 19 autologous transplants. Ten allogeneic patientssuffered from severe acute graft-versus-host diseases (GVHD),and extensive chronic GVHD appeared in 16 patients. Relapseswere observed in four cases of allogeneic BMT and six of autologous.BMT. The major complications were interstitial pneumonitis (IP)and severe infections. Long-term, survival rates were almost60% in both allogeneic and autologous transplants. Mild acuteGVHD and limited chronic GVHD increased the survival rates.The results indicated that substantial problems such as GVHD,IP and relapses must be controlled in the near future for animproved outcome to be made possible.     

Prediction of patient discomfort during fibreoptic bronchoscopy

OBJECTIVE: This study investigated the potential for predicting which patients would have a negative emotional reaction to bronchoscopy. METHODOLOGY: A questionnaire was distributed to 120 patients who had undergone diagnostic fibreoptic bronchoscopy. A visual analog scale to evaluate the patient's discomfort was adopted. Multiple linear regression analysis was used to determine factors significantly influencing discomfort. The regression model included the following variables: age, gender, symptoms, smoking habits, proximal bronchial brushing, distal bronchial brushing, bronchial washing, proximal transbronchial biopsy, transbronchial lung biopsy, examination time, the bronchoscopist's experience, and the patient's anxiety level. RESULTS: The bronchoscopist's experience (P = 0.001) and the patient's anxiety level (P < 0.001) were variables that significantly influenced discomfort. These results suggest that discomfort decreased with the bronchoscopist's experience and increased with the patient's anxiety regarding bronchoscopy. CONCLUSIONS: The results suggest that subjective discomfort can be predicted both by the bronchoscopist's experience and by a questionnaire about the patient's anxiety level before bronchoscopy. Therefore, it is recommended that the patient's anxiety level be determined through the use of a questionnaire before bronchoscopy, and that more experienced bronchoscopists should take charge if the patient is judged as being excessively anxious. If experienced bronchoscopists are unavailable, the more anxious patient should receive more sedatives.