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.     

Malignant carcinoid of the pancreas: a cytologic, ultrastructural, and immunocytochemical study of a case diagnosed by fine-needle aspiration of a supraclavicular node metastasis

Carcinoid tumor of the pancreas is extremely rare. This article describes the case of a 22-year-old woman who manifested a typical carcinoid syndrome; a definitive diagnosis of a metastatic carcinoid tumor was made from needle aspiration of a supraclavicular lymph node using morphologic, immunocytochemical, and ultrastructural criteria. The carcinoid tumor was subsequently shown to be of pancreatic origin.     

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.     

Outcome of laparoscopic ventral hernia repair in correlation with obesity,type of hernia,and hernia size

BACKGROUND: The morbidity and overall recovery time of ventral hernia repair can vary significantly depending on the hernia type or size and on other factors, such as the body mass index (BMI). The purpose of our study was to investigate the effects of type of hernia, hernia size, and BMI on the outcome of laparoscopic ventral hernia repair. METHODS: Fifty patients who underwent laparoscopic ventral hernia repair were retrospectively reviewed and stratified according to hernia type (incisional, IVH/primary, PVH), hernia size, and BMI. These subgroups were compared in regard to operative time, resumption of diet, hospital stay, pain control, and complication rate. RESULTS: Laparoscopic IVH repair was associated with a longer operative time (143 vs. 98 minutes, p = .02) and length of stay (2.2 vs. 0.6 days, p = .03) than PVH repair. The narcotic requirements were higher in the IVH group, but the difference did not reach statistical significance. Larger hernias were associated with a longer operative time (p = .04) and increased narcotic requirement (p = .03). The morbidity of the laparoscopic repair was not significantly affected by the hernia type or size. The BMI did not significantly alter any of the parameters examined. CONCLUSIONS: Laparoscopic repair of incisional and larger hernias is a technically demanding procedure that requires a longer operative time. In contrast to PVH repair, laparoscopic IVH repair usually cannot be performed on an outpatient basis. Surgeons need not be discouraged from recommending the laparoscopic approach for patients with large IVHs or with severe obesity because the morbidity remains low.     

A phase Ib/II trial of granulocyte-macrophage-colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastases: a case of fatal central nervous system thrombosis

BACKGROUND: Interleukin-2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL-2 plus GM-CSF. METHODS: Patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 x 10(6) IU/m(2)/day 96-hour continuous infusion IL-2 on Days 1-4, 8-11, and 15-18, and 1.25, 2.25, or 2.5 microg/kg/day GM-CSF on Days 8-19. RESULTS: Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had >50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. Autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage. CONCLUSIONS: The combination of IL-2 and GM-CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL-2 and GM-CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity.     

Central venous device-related infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2

BACKGROUND: This study was performed to determine the incidence of central venous device-related blood stream infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2 (IL-2). METHODS: The records of 160 consecutive patients treated at the University of Wisconsin Hospital and Clinics, between June 1990 and June 1997, with moderate dose continuous-infusion IL-2 (IL-2 [1.5-3.0 x 10(6) U/m(2)/day] Hoffman-LaRoche, Nutley, NJ or IL-2 [4.5 x 10(6) U/m(2)/day] Chiron Corporation, Berkley, CA) were reviewed retrospectively. The majority of patients had metastatic melanoma (78 patients) or renal cell carcinoma (70 patients). All of the patients had a surgically implanted central venous device placed before starting IL-2 therapy; 89% of these were cuffed Hickman catheters. Eighty-four patients received 1 mg of warfarin per day as prophylaxis against device-related thrombosis; none received periinsertion prophylactic antibiotics. RESULTS: Twenty-one patients (13%) developed central venous device-related bloodstream infection (DRBSI) during the study period, a rate of 2 DRBSI per 1000 device-days. DRBSIs were associated with the type of immunotherapy given with IL-2 (P = 0.01) and with thrombosis (odds ratio, 4.1; 95% confidence interval, 1.5-11.4; P = 0.008) but not with patient gender, type of cancer, duration of the central device, or site of device placement. Twenty-six patients (16%) developed central venous device-related thrombosis (DRT) during immunotherapy. Low dose warfarin did not appear to prevent thrombosis. Device-related thrombosis was associated with DRBSI but not with patient gender, type of cancer, type of device, duration or location of device, or concomitant immunotherapy. CONCLUSIONS: Central venous DRBSI and DRT are significant complications that can occur during moderate dose continuous-infusion IL-2 therapy. The risk of DRBSI appears lower than the risk reported with high dose IL-2 therapy by previous investigators. The risk of DRT appears to be higher than the risk reported for patients with similar devices but not given IL-2. Low dose warfarin did not prevent DRT when started after device placement.     

Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations.

Interleukin-2 (IL-2) is a potent lymphokine that activates natural killer cells, T cells, and other cells of the immune system. Several distinct recombinant human IL-2 preparations have shown antitumor activity, particularly for renal cell cancer and melanoma. Somewhat distinct immune and clinical effects have been noted when different IL-2 preparations have been tested clinically; however, the regimens and doses used were not identical. To compare these more directly, we have evaluated two clinical recombinant IL-2 preparations in vitro and in vivo using similar regimens and similar IUs of IL-2. We used the Food and Drug Administration-approved, commercially available Chiron IL-2 and the Hoffmann LaRoche (HLR) IL-2 supplied by the National Cancer Institute. Using equivalent IUs of IL-2, we noted quantitative differences in vitro and in vivo in the IL-2 activity of these two preparations. In patients receiving comparable IUs of the two preparations, HLR IL-2 induced the release of more soluble IL-2 receptor alpha into the serum than Chiron IL-2. In addition, more toxicities were noted in patients receiving 1.5 x 10(6) IU of HLR IL-2 than were seen in patients treated with 1.5 x 10(6) or even 4.5 x 10(6) IU of Chiron IL-2. These toxicities included fever, nausea and vomiting, and hepatic toxicity. In vitro proliferative assays using IL-2-dependent human and murine cell lines indicated that the IU of HLR IL-2 was more effective than Chiron IL-2 at inducing tritiated thymidine incorporation. Using flow cytometry, we also found quantitative differences in the ability of these two preparations to bind to IL-2 receptors. These findings indicate that approximately 3-6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.     

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.