The myocardial performance index during low-dose dobutamine echocardiography in control subjects and patients with a recent myocardial infarction: a new index of left ventricular functional reserve?

BACKGROUND: Wall-motion analysis during low-dose dobutamine echocardiography (LDDE) is a semiquantitative measure of left ventricular contractile reserve after myocardial infarction (MI). The Doppler echocardiographic myocardial performance index (MPI) is a quantitative measure of combined left ventricular systolic and diastolic function. We sought to characterize the changes in MPI during LDDE in control subjects and patients with MI, and to describe the relation of these changes to changes in regional systolic function. METHODS: MPI was obtained at rest and during LDDE (10 microg/kg/min) in 25 healthy volunteers (group 1) and 50 patients with a recent MI. Patients were divided into two subsets; those with (n = 23; group 2A) and those without (n = 27; group 2B) a contractile reserve defined as an improvement of wall motion in more than two contiguous infarct-zone segments during LDDE. DeltaMPI was defined as the change from rest to LDDE. RESULTS: MPI decreased significantly during LDDE in groups 1 and 2A, whereas MPI increased in group 2B (DeltaMPI = 0.12 +/- 0.04 and 0.10 +/- 0.08 vs -0.03 +/- 0.08, P <.0001). On multivariate analysis, Deltawall-motion score index predicted DeltaMPI (beta = 0.65, P <.0001) independently of age, sex, and the dobutamine-induced change in heart rate and systolic blood pressure. CONCLUSIONS: Data suggest that the change in MPI during LDDE may provide a simple and quantitative measure of overall left ventricular functional reserve in patients with a recent MI.     

The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies.

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.     

Case report: Management of immediate post-car-diopulmonary bypass massive intra-cardiac thrombosis

PURPOSE: To describe the management of severe acute intracardiac thrombosis in a patient who underwent redo multiple valve replacement and valvular repair. The diagnostic features, associated risk factors, and anesthetic management are reviewed. CLINICAL FEATURES: A 67-yr-old woman undergoing redo mitral and aortic mechanical valve replacement and tricuspid annuloplasty under aprotinin prophylaxis exhibited severe refractory hypotension that began immediately after protamine reversal of intraoperative heparin anticoagulation following separation from cardiopulmonary bypass. Intraoperative transesophageal echocardiography revealed severe thrombosis in the right atrium, right ventricle and pulmonary artery. The patient was managed by immediate reheparinization and return to cardiopulmonary bypass (CPB), surgical thrombectomy, and intraoperative administration of recombinant tissue-plasminogen activator. After removal of the thrombi, and separation from CPB, no further protamine was given. One hundred units of blood products and two surgical re-explorations were required to manage subsequent massive postoperative bleeding. Acute heparin-induced thrombocytopenia (HIT) was ruled out using sensitive assays for HIT antibodies. After 16 days in the intensive care unit and 30 more days in hospital, the patient was subsequently transferred to a chronic care facility and succumbed several weeks later. CONCLUSION: Acute intraoperative thrombosis is a rare and potentially fatal complication of cardiac surgery. Intraoperative transesophageal echocardiography was essential for rapid diagnosis in this case. Multiple interacting prothrombotic factors (e.g., aprotinin use, acquired antithrombin deficiency, long pump time, post-protamine status, transfusion of blood components) were likely contributing factors related to this rare complication.     

18F-FDG PET can replace conventional work-up in primary M staging of nonkeratinizing nasopharyngeal carcinoma.

Conventional work-up (CWU) with chest radiography, abdominal ultrasonography, and skeletal scintigraphy has limited value in M staging of nonkeratinizing nasopharyngeal carcinoma (NPC). Our aim was to evaluate whether (18)F-FDG PET could replace CWU by comparing their diagnostic efficacies. METHODS: Patients with histologically proven nonkeratinizing NPC and no prior treatment were prospectively enrolled. All study participants underwent CWU and (18)F-FDG PET for primary M staging. Distant metastasis was considered to be present if there was any reliable evidence identified within 1 y after diagnosis. The comparative diagnostic efficacies of (18)F-FDG PET, CWU, and the combination of (18)F-FDG PET and CWU (PET+CWU) were evaluated using the areas under the receiver-operating-characteristic (ROC) curves. RESULTS: Sixty-one (20.3%) of 300 eligible patients were found to have distant metastases. On a patient-based analysis, (18)F-FDG PET was found to be more effective than CWU (P < 0.001), whereas it was equally effective with PET+CWU (P = 0.130). On region-based analyses, (18)F-FDG PET was more effective than skeletal scintigraphy and chest radiography for detecting bone metastases (P < 0.001) and chest metastases (P < 0.001), respectively. (18)F-FDG PET and abdominal ultrasound were equally effective for detecting hepatic metastases (P = 0.127). On region-based analyses, the combination of (18)F-FDG PET and CWU did not yield any noticeable increase in diagnostic efficacy. CONCLUSION: (18)F-FDG PET can replace CWU in primary M staging of nonkeratinizing NPC.     

Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions.     

The effects of altering time delays of coupled pacing during acute atrial fibrillation

BACKGROUND: Coupled pacing (CP), which consists of delivering a premature electrical stimulation to the heart after the effective refractory period of ventricular activation, is a novel method for controlling ventricular rate during atrial fibrillation (AF). It also has been established that CP improves pump function by enhancing external cardiac work and myocardial efficiency. OBJECTIVE: The purpose of the present study was to determine if two time delays for CP (short and long) would result in similar improvements in ventricular function. METHODS: In a canine model, we applied CP at two time delays (CP-S and CP-L) during two stages: sinus rhythm (SR) and acute AF. The cardiac responses to CP during SR served as the nontachycardic and nondepressed control. During both rhythms, we shortened the coupling interval until we obtained maximal contractility, designated CP-S. Next, we increased the delay until we started to see a measurable secondary contraction (left ventricular pressure development of approximately 20 mmHg). These longer delays were designated CP-L. RESULTS: Our results showed that the ventricular rate of intrinsic activation (VRIA) remained decreased despite prolongation of the time delay of CP during both AF and SR. Also, both delays of CP increased left ventricular systolic pressure (LVSP) and dLVP/dt, which are indices of myocardial contractility. In contrast, CP increased external cardiac work only during AF. Prolonging this time delay did not markedly decrease the improvement in external cardiac work. Myocardial O(2) consumption (MVO(2)) did not significantly change as the result of CP during either SR or AF. Finally, myocardial efficiency improved during AF as the result of CP at both time delays. CONCLUSIONS: In conclusion, shorter time delays for CP increased contractile strength during both SR and AF. However, extending the time delay of CP had minimal effects on diminishing the improved ventricular pump function and energetics that resulted from CP during AF. Thus, the maximal enhancement of myocardial contractility via CP-S was not needed to maintain the improved ventricular function during acute AF when CP is applied.     

The effects of illicit drug use and HIV infection on sex hormone levels in women.

Drug use and HIV infection may affect sex hormone levels in women. One hundred and ninety-six women with and without a history of illicit drug use (50 HIV-negative and 148 HIV-infected), with regular menses, who never used antiretrovirals, were evaluated. Luteinizing hormone levels were significantly higher in women with a CD4 cell count <200/microl (p < 0.002). Current methadone use was associated with lower levels of total testosterone (p = 0.03) and higher levels of prolactin (p = 0.002); mean estradiol levels were 43% lower in women who used intravenous drugs (p < 0.001). Alcohol and crack cocaine use was not associated with sex hormone levels. Age, race, body mass index and degree of HIV immunosuppression were also associated with differences in sex hormone levels.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.