Doppler echocardiography of 119 normal-functioning St Jude Medical mitral valve prostheses: a comprehensive assessment including time-velocity integral ratio and prosthesis performance index.

The purpose of this study was to provide, in a large number of patients, comprehensive Doppler echocardiographic assessment of normal St Jude Medical mitral valve prosthesis function using Doppler-derived hemodynamic variables, including the mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio and prosthesis performance index. The pressure half-time was less than 130 milliseconds in all patients, and all but one patient had either a peak early mitral diastolic velocity of 2 m/s or less or a mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio of less than 2.2. There was a significant (P < .001) negative correlation between the prosthesis performance index and prosthesis size. This negative correlation suggests that there is more efficient use of the in vitro geometric orifice area with smaller prostheses.     

Combining Vaccines with Conventional Therapies for Cancer

Preclinical and clinical investigations currently underway are employing novel strategies for combining vaccines with conventional and experimental anticancer therapies. To date, the FDA has not approved a therapeutic cancer vaccine. However, the results of recent investigations suggest an increasing role for vaccines in new models of combination therapy for many types of cancer. This article reviews and discusses therapeutic cancer strategies that employ vaccines in combination with local radiation, chemotherapy, hormone therapy, and anti-CTLA-4 mAb. Preclinical studies have shown that certain anticancer agents have immune modulatory effects that result in up-regulation of surface expression of MHC molecules, tumor-associated antigens, or Fas on malignant cells, rendering them more susceptible to immune destruction. Preliminary results of clinical studies using combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and improved overall survival. Several larger randomized trials are ongoing, and more are required to support these findings.     

Surface activation markers of T lymphocytes: role in the detection of infection in neonates

Diagnosis of perinatal infection in the newborn is difficult; there may be few clinical signs and current tests are slow or non-specific. Detection of organisms, antigen or specific antibody to common pathogens often requires repeat samples and does not give immediate results. Haematological parameters, although relied upon frequently to diagnose infection in the neonate prior to a positive bacterial isolation, are unreliable and insensitive. Indicators such as an increase in neutrophil band cell counts are highly variable between morphologists. Infection induces the expression of a number of T lymphocyte surface markers, including CD45RA/CD45RO and CD45RO. The use of changed expression of surface markers as a laboratory test for detection of infection in neonates was evaluated. We used multiparameter flow cytometry to detect expression of early (CD45RA/CD45RO) and late (CD45RO) activation markers. In the respective groups of 50 full term (including 25 normal vaginal deliveries and 25 caesarean deliveries) and 30 premature, i.e. < 36 weeks gestation (born by either normal vaginal delivery or caesarean delivery) the CD45RA isoform was brightly expressed on newborn ‘naive’ CD4⁺ T cells, whereas the CD45RO isoform (including both ‘bright’ and ‘dim’ populations) was present on < 19% of CD4⁺ T cells from these newborn infants. In a group of 37 infants, tested to evaluate possible effects of non-infective parameters such as respiratory distress and iso-immunization, no significant changes in surface marker expression were found and specificity of the test was confirmed. In 14 neonates with documented sepsis, up-regulation of dual staining CD45RA/CD45RO isoforms on CD4⁺ T cells was detected early in the infection. In addition, we found that CD45RO expression persisted for several weeks after bacterial infection, and up to several months in viral infection. In conclusion, detection of T cell activation by flow cytometry for the early diagnosis of neonatal infection is an easy test to carry out on small volumes of blood, is inexpensive, and may be a specific indicator of infection.     

Effects of morphine on acquisition and maintenance of ethanol and water intake patterns in rats.

Two experiments were conducted to assess the effects of chronic subcutaneous injections of morphine (1.0 mg/kg) or saline on the pattern and amount of sweetened ethanol and water intake in fluid restricted Long-Evans rats. Following daily injections, 2-h two-bottle choice tests were conducted with water and an ethanol solution (15% ethanol v/v in 5% sucrose w/v). During a 20-day acquisition phase (Experiment 1), ethanol intake patterns and amounts did not differ between saline (n = 6) and morphine (n = 6) groups. Both groups exhibited ethanol intake patterns that decreased exponentially throughout the session suggesting control by fluid restriction procedures. Morphine decreased water intake during initial periods of each session and increased intake during later periods. In Experiment 2, morphine and saline injections were reversed across three phases with the same rats. Morphine increased total ethanol consumption during the first few days of each 15-day phase, but the groups did not differ thereafter, and the initial increases produced no statistically significant group differences. Additionally, morphine augmented ethanol intake in early portions of sessions, while water intake was decreased and increased during early and later portions of each session, respectively. Analysis of the data from the last 5 days of each phase indicated that, when injected with morphine, the group which received saline during acquisition consumed significantly more ethanol solution than the group injected with morphine during acquisition. The effect on patterns of water and ethanol intake were observed, regardless of the drug injected during acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)     

The value of myocardial perfusion single-photon emission computed tomography in screening asymptomatic patients with atrial fibrillation for coronary artery disease.

OBJECTIVES: We sought to determine if screening for coronary artery disease (CAD) with stress single-photon emission computed tomography (SPECT) is of value in patients with atrial fibrillation (AF) who do not have symptoms of chest pain or dyspnea. BACKGROUND: Although noninvasive stress testing is often done to screen for CAD in asymptomatic patients with AF and is considered to be appropriate in selected patients, its potential utility has not been demonstrated. METHODS: A retrospective study was conducted of 374 asymptomatic patients with AF referred for the detection of CAD. Mean follow-up was 5.7 +/- 3.8 years. The study group was compared with a control group of 374 asymptomatic age and gender-matched patients without AF. RESULTS: The mean summed stress score (SSS) was not significantly different between AF patients and control subjects (3.6 +/- 5.3 vs. 3.5 +/- 5.9; p = 0.35). Compared with controls, asymptomatic AF patients had similar rates of abnormal SPECT studies (51.6% vs. 48.4%; p = 0.38) and high-risk studies (14.4% vs. 14.4%; p = 1.0). The SSS was a significant predictor of outcome in both AF patients and control subjects. However, total mortality was significantly greater in AF patients (5-year overall mortality 27% vs. 18%, 10-year overall mortality 47% vs. 40%; p < 0.001), and this difference persisted (p = 0.01) after adjusting for multiple clinical variables and the SSS. CONCLUSIONS: Screening for CAD using stress SPECT in asymptomatic AF patients has a yield similar to age- and gender-matched control patients without AF. Although SSS predicts mortality in patients with and without AF, patients with AF have increased total mortality independent of the findings on stress SPECT. These results suggest that factors other than obstructive CAD are responsible for the increased mortality in AF.     

Osteogenic Sarcoma of the Left Atrium

A primary cardiac osteogenic sarcoma is described in a patient presenting with a left atrial obstructive lesion. Wide surgical excision was possible with left atrial reconstruction and mitral valve replacement. The patient survived the operation and was symptom free for 1 year, finally dying at 18 months of cerebral metastases.