Selecting the Best Noninvasive Imaging Test to Guide Treatment After an Inconclusive Exercise Test

The first step towards approaching a patient with an inconclusive stress test is to identify the initial reason why a stress test was ordered and examine what factors led to inconclusive test results. Next, it is important to ask whether the patient will benefit from further testing, as not all patients with inconclusive test results require additional testing. In patients who are at low-to-intermediate risk, it may be useful to perform coronary CT angiography (CTA) to exclude the presence of obstructive coronary atherosclerosis. Among individuals with no prior history of coronary artery disease, a possible advantage of CTA is that if subclinical atherosclerosis is identified, intensification of lifestyle interventions, and often pharmacotherapy, should be advocated. On the other hand, in high-risk patients or individuals that already have coronary artery disease, the primary objective is to quantify the presence and magnitude of ischemia in order to define the potential role of coronary revascularization procedures. This can be achieved by myocardial perfusion imaging using nuclear imaging or cardiac MRI. Alternatively, a functional evaluation to identify stress-induced wall motion abnormalities using stress echocardiography or MRI can be obtained. In selecting which test to obtain, it is important to understand the strengths and limitations of different imaging tests and to consider patient factors (e.g., body habitus) that may influence the accuracy of various tests. In addition, physicians should consider whether there are any other clinical questions that require imaging. For instance, cardiac MRI may be used to evaluate for infiltrative myocardial disease or pericardial disease whereas cardiac CT can evaluate for lung pathology or diseases of the aorta. Finally, any decision regarding what type of additional testing to obtain should also be based on knowing the local expertise and availability of various testing options.     

Sleep-related epilepsy in a Long-Evans hooded rat model of depression

Introduction

Neonatal treatment with clomipramine (CLI) has been shown to have reliable behavioral and biological changes that mimic major symptomatic and biochemical changes found in depression. This paper further explores a common feature of depression, the comorbidity of seizure activity and depressive behaviors in this mode.

Methods

Rat pups were neonatally treated with 40?mg/kg/day of CLI from postnatal day 8 through 21. In adulthood, they were instrumented with electroencephalographic (EEG) and electromyographic (EMG) electrodes for 24?h of polysomnogram (PSG) recordings. PSG data were analyzed for: (1) sleep-wake cycle; (2) spectral power; and (3) epileptiform activity, including NREM-to-REM transition (NRT) bursts.

Results

Neonatal treatment with CLI reliably produces enhanced levels of REM (p?<?0.01) and reduced sexual activity (p?<?0.05). Theta power was enhanced during NREM sleep in the CLI group (p?=?0.02). CLI-treated animals experienced increased frequency at the NRT (p?<?0.01), as well as additional epileptiform activity of continuous (CTS; p?<?0.05) and petite-continuous (P-CTS; p?<?0.01) types, across the sleep?Cwake cycle. There is a strong temporal correlation with increased REM sleep duration, increased frequency of NRT bursts, and increased theta power during NREM sleep in CLI-treated animals.

Discussion

Neonatal CLI-treated animals experienced significantly more epileptiform activity as a whole, in addition to comorbid features of depression in adulthood. Neonatal exposure to CLI will not only produce depressive phenotype but may also enhance risk for epilepsy in some individuals. This warrants further investigation into currently acceptable medicinal use in humans.     

Subclinical anthracycline cardiotoxicity in patients with acute promyelocytic leukemia in long-term remission after the AIDA protocol

Anthracycline chemotherapy remains a critical component of cancer treatment despite its established risk of cardiotoxicity. To investigate whether the AIDA protocol, which combines idarubicin, mitoxantrone, and all-trans retinoic acid (ATRA) for treatment of acute promyelocytic leukemia (APL) results in late cardiotoxicity, 34 APL patients in long-term remission were evaluated. The cumulative dose of idarubicin and mitoxantrone were 80 mg/m(2) and 50 mg/m(2), respectively. Median follow-up was 7 years. Segmental wall motion abnormalities (SWMAs) were detected in 11 AIDA patients who still presented with an ejection fraction (EF) within normal limits (EF 56% in the AIDA group vs 59% in the control group, P=.01). However, parameters of diastolic dysfunction were significantly impaired in the AIDA group (E/A ratio: 1.04 in the AIDA group vs 1.28 in the control group, P=.001; E/E' lateral ratio: 10.04 in the AIDA group vs 5.79 in the control group, P≤.001) as well as left atrial volume (52 mL in the AIDA group vs 35 mL in the control group, P<.001). Cardiac toxicity due to anthracycline therapy is often frequent. Changes in diastolic function are helpful in the detection of subclinical anthracycline cardiotoxicity in long-term cardiac follow-up despite a preserved systolic ventricular function.     

Predictors of Mortality in Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae: Importance of Combination Therapy

Background.?The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians. Methods.?In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. Results.?The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P?=?.02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P?=?.008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P?=?.003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P?相似文献   

Potential mechanisms for increased HIV-1 transmission across the endocervical epithelium during C. trachomatis infection

Among the now pandemic sexually transmitted infections (STIs), Chlamydia trachomatis (C. trachomatis) is the predominant bacterial pathogen and human immunodeficiency virus type 1 (HIV-1) is the most lethal of the viral pathogens. The female genital tract is the primary site for heterosexual transmission of both C. trachomatis and HIV-1. Infection with C. trachomatis, and with a variety of other STIs, increases the risk for transmission of HIV-1, although the mechanisms for this finding remain unclear. We have used in vitro modeling to assess the mechanisms by which infection with genital C. trachomatis serovars might increase the transmission of HIV-1 across the female genital tract. C. trachomatis infection of an immortalized endocervical epithelial cell line (A2EN) increases the cell surface expression of the HIV-1 alternative primary receptor, galactosyl ceramide (GalCer), and of the HIV-1 co-receptors, CXCR4 and CCR5. C. trachomatis infection also increases the binding of HIV-1 to A2EN cells, and, subsequently, increases levels of virus in co-cultures of HIV-exposed A2EN and susceptible MT4-R5 T cells. Finally, in vivo endocervical cell sampling reveals a dramatic increase in the number of CD4+, CXCR4 and/or CCR5 positive T cell targets in the endocervix of C. trachomatis positive women when compared to those who are C. trachomatis negative. This combination of in vitro and in vivo results suggests several mechanisms for increased transmission of HIV-1 across the endocervices of C. trachomatis-infected women.