Electromechanical properties of perfusion/metabolism mismatch: comparison of nonfluoroscopic electroanatomic mapping with 18F-FDG PET.

The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue. METHODS: Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion. RESULTS: Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001). CONCLUSION: In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures.     

Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model

Background

Endotoxemia is a major cause of mortality in large animals and there are several therapeutic regimens for the treatment of endotoxemia. Recent studies have suggested the anti-inflammatory effects of insulin in endotoxemic human and laboratory animal models but to the best of our knowledge there is no report on the possible therapeutic effect of insulin in large animal endotoxemia.

Objective

This experiment was conducted to evaluate the anti-inflammatory effects of insulin regular compared with flunixin meglumine on the treatment of endotoxemia in sheep.

Methods

Lipopolysaccharide from Escherichia coli was administered intravenously to ewes. Anti-inflammatory effects of flunixin meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated by determination of serum concentrations of acute phase proteins, inflammatory cytokines and oxidative stress biomarkers.

Results

Insulin regular at 3 IU/kg controlled the acute phase response following endotoxemia induction. The anti-inflammatory potency of insulin regular at 3 IU/kg was significantly higher than at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg (P < 0.05).

Conclusion

Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine.     

Cardiac Outcomes Through Digital Evaluation (CODE) STEMI project: prehospital digitally-assisted reperfusion strategies

Background

Guidelines for reperfusion in ST-elevation myocardial infarction (STEMI) were recently adopted by the Canadian Cardiovascular Society. We have developed a blended model of prehospital thrombolytic (PHL) therapy or primary percutaneous coronary intervention (PPCI) activation, in order to achieve guideline times.

Methods

In our urban centre of 658,700 people, emergency medical services (EMS) were trained to perform and screen electrocardiograms (ECGs) for suspected STEMI. Suspected ECGs were transmitted to a physician's hand-held device. If the physician confirmed the diagnosis they coordinated initiation of either PHL or PPCI. In cases where physicians found the prehospital ECG negative for STEMI (PHENST), patients were transported to the closest emergency room.

Results

From July 21, 2008 to July 21, 2010, the Cardiac Outcomes Through Digital Evaluation (CODE) STEMI project received 380 transmitted calls. There were 226 confirmed STEMI by the on-call physician, 158 (70%) received PPCI, 48 (21%) received PHL, and 20 (9%) had angiography but no revascularization. The PPCI, median time from first medical contact to reperfusion was 76 minutes (interquartile range [IQR], 64-93). For PHL, median time from first medical contact to needle was 32 minutes (IQR, 29-39). The overall mortality rate for the STEMI patients was 8% (PHL = 4 [8.3%], PPCI = 8 [5%], medical therapy = 7 [35%]). There were 154 PHENST patients, 44% later diagnosed with acute coronary syndrome. The mortality rate for PHENST was 14%.

Conclusions

Through a model of EMS prehospital ECG interpretation, digital transmission, direct communication with a physician, and rapid coordinated service, we demonstrate that benchmark reperfusion times in STEMI can be achieved.     

Mercury exposure among residents of a building block in Shiraz, Iran

Exposure to mercury can cause serious multiorgan damage affecting the central nervous system, kidneys, liver, lungs, spleen, bone marrow, and skin. At the end of the summer of 1999, the accidental leakage of 4 liters of mercury from a container into the waterway canals resulted in mass exposure to elemental mercury among the residents of a building block of a residential area of the city of Shiraz, in the south of Iran. One hundred and eleven individuals who experienced exposure to elemental mercury were investigated. Twenty-four-hour measurement of the urine mercury level-revealed a toxic level of more than 20 microg/L in 6 children and 3 adults (including a pregnant woman). Despite normal physical and laboratory (CBC, renal and liver function tests, and urinalysis) findings, dimercaprol was prescribed. One month later during the course of the follow-up the urine mercury level in 6 patients, including the pregnant woman from the same family, was found to be again at a toxic level. The pregnant mother from the same family aborted her fetus; however, due to the lack of equipment for measuring the serum mercury level, it was not possible to confirm the relation between the mercury toxicity and the abortion. This family had kept mercury in their kitchen against health workers' instructions. The attractive physical and chemical properties of mercury could explain the continuity of exposure and poisoning in these 6 cases. It is concluded that prophylactic therapy in the presence of toxic levels of mercury, despite the presence of an asymptomatic state in exposed residents, is effective in preventing the development of signs and symptoms, though instruction of high-risk cases is the best way to combat it.     

Health-related quality of life after chemotherapy cycle in breast cancer in Iran

The aim of this study was to compare the differences between the level of whole quality of life and its subscales after receiving two common treatment of breast cancer in women with early stage of breast cancer. A double-blinded cohort study was done in 100 breast cancer patients with node positive that used fluorouracil, doxorubicin, cyclophosphamide (FAC) and docetaxel, doxorubicin and cyclophosphamide (TAC) regimen as adjuvant therapy. Patients were followed for 4 months since the end of chemotherapy. Health-related quality of life was assessed using questionnaire (QLQ-C30) from European Organization for Research and Treatment of Cancer (EORTC). Independent t-test analysis was used at the significant level of 0.05 for analyzing the results. The mean of age was 48.49 ± 10.63 in these patients. QoL scores were 64 and 68 in TAC and FAC groups, respectively (P < 0.001). After 4 months, patients in TAC and FAC groups experienced 11.45 and 7.14 units of improvement in QoL scores, respectively (P = 0.02). Although, TAC had a more negative impact on QoL during chemotherapy, it created a higher improvement than FAC during 4 months since the end of treatment. These effects on quality of life should be considered in making decision for providing and financing cancer treatments in Iran.

     

hOGG1 gene polymorphism and breast cancer risk: A systematic review and meta‐analysis study

To address the effect of hGGO1 (rs1052133) gene polymorphism on the risk of breast cancer, a meta‐analysis was performed. We pooled adjusted odds ratios (OR) as overall and three subgroups (menopausal status, ethnicity, and study setting). In overall analysis, we found a significant association when the model of inheritance was homozygote (pooled OR 1.14; 95% CI 1.01, 1.29). Subgroup analysis showed significant association for homozygote genetic models among postmenopause women (OR 1.23; 95% CI 1.01, 1.49) and Asian population (OR 1.17; 95% CI 1.01, 1.35). This study suggested that the carrier of Ser326Cys polymorphism of hOGG1, Cys/Cys vs Ser/Ser, are at higher risk for breast cancer, independent of other hormonal and environmental risk factors.     

Combination therapy of rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, and NMDA receptor antagonist (MK-801) on experimental embolic stroke in rats

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been found to have potent anti-inflammatory actions and suggested as potential therapies for brain ischaemia. Glutamate is the most common excitatory neurotransmitter in the central nervous system and is released excessively during ischaemia. Stroke therapy will require combinations of drug classes, because no single drug class has yet been proven efficacious in human beings. The present study was conducted to assess whether N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment can improve recovery from ischaemic brain injury and whether rosiglitazone, a PPAR-gamma ligand, can increase its neuroprotective effect in an embolic model of stroke. Stroke was induced in rats by embolizing a preformed clot into the middle cerebral artery. Rosiglitazone (0.1 mg/kg, intraperitoneally) and MK-801 (0.1 mg/kg, intravenously) were injected immediately after embolization. Forty-eight hours later, the brains were removed, sectioned and stained with triphenyltetrazolum chloride and analysed by a commercial image processing software programme. Rosiglitazone and MK-801 alone or in combination decreased infarct volume by 49.16%, 50.26% and 81.32%, respectively (P < 0.001). Moreover, the combination therapy significantly decreased the infarct volume when compared to any drug used alone (P < 0.05). MK-801 reduced the brain oedema by 68% compared to the control group (P < 0.05), but rosiglitazone or combination did not show any significant effect. The drugs alone or in combination also demonstrated improved neurological function, but combination therapy was more effective on neurological deficits improving. Our data show that the combination of MK-801 and rosiglitazone is more neuroprotective in thromboembolic stroke than given alone; this effect perhaps represents a possible additive effect in the brain infarction.     

Typical chest pain and normal coronary angiogram: cardiac risk factor analysis versus PET for detection of microvascular disease.

Angiography of patients with typical chest pain reveals normal epicardial coronary arteries in about 20%. Coronary flow reserve (CFR) determination is an elaborate, but helpful, task, as only the evidence of microvascular disease enables appropriate therapy. We prospectively evaluated the incidence of a dysfunctional microcirculation and searched for predictive parameters of a reduced CFR. METHODS: In 79 consecutive patients (52 females, 27 males) with typical angina and a normal angiogram and 10 control subjects (6 females, 4 males), CFR was measured by 13N-ammonia rest/dipyridamole PET and correlated with clinical parameters individually and summarized as the number of risk factors (NRF) using an elaborated cardiac risk factor score. RESULTS: Sixty-five percent of patients had a reduced CFR (CFR < 2.5). CFR correlated with NRF (r = 0.55, P < 0.001), systolic blood pressure (r = 0.46, P < 0.001), interventricular septal thickness (r = 0.33, P < 0.01), and age (r = 0.25, P = 0.02). Eighty-five percent of patients with a high risk factor score (NRF > or = 5) had a reduced CFR. In contrast, 100% of our patients with a low risk factor score (NRF < 2) presented a normal CFR. In total, 55% of our patients could be allocated to either one of these groups. CONCLUSION: In about two thirds of patients, anginal pain can be explained by a reduced CFR. Risk factors have a cumulative negative effect on CFR. A clinical cardiac risk factor analysis enables estimation of individual probability of microvascular dysfunction in a significant proportion of these patients. However, CFR measurements are recommended for those with an intermediate NRF.     

Automated assessment of myocardial SPECT perfusion scintigraphy: a comparison of different approaches of case-based reasoning

OBJECTIVE: This study compared the diagnostic accuracy of different approaches of case-based reasoning (CBR) for the assessment of coronary artery disease (CAD) using thallium-201 myocardial perfusion scintigraphy in comparison with coronary angiography. METHODS AND MATERIAL: For each scintigraphic image set, regional myocardial tracer uptake was obtained by polar map analysis. CBR algorithms based on a similarity measure were employed to identify similar scintigraphic images within the case library, where each case contained the scintigraphic data together with results of coronary angiography. The angiographic data of retrieved cases were then used to determine whether significant CAD was present in one of the major coronary arteries. Three different approaches of CBR were compared: (1) case retrieval based on a global comparison of polar map data (GLOB), (2) case retrieval based on a territorial comparison of polar map data (TER), and (3) case retrieval based on a comparison of a given case with eight sub-libraries classified according to the involvement of the three major coronary vessels using a group similarity measure (GROUP). Two matching algorithms the best-match approach and an adapted retrieving approach were combined with all three case retrieval methods and their influence on the diagnostic accuracy were investigated. RESULTS: For overall detection of significant CAD, the best-match approach of both TER and GROUP retrieval methods showed a higher diagnostic accuracy than the GLOB retrieval method (75% and 77% versus 70%, respectively). ROC analysis for the adapted retrieving approach showed a similar diagnostic accuracy for all three methods with an area under the curve of 0.79, 0.8, and 0.8 for GLOB, TER, and GROUP, respectively. CONCLUSION: The observed improvement in the diagnostic accuracy by the new approaches may lead to further improvements of CBR systems, which have the potential to offer valuable decision support for human readers, especially for less experienced investigators.