Doppler myocardial imaging: A new method of data acquisition for three-dimensional echocardiography

The precise morphologic characteristics of any intracardiac tumor have important implications regarding surgical planning and operative repair. Three-dimensional echocardiography has proved to be a valuable clinical technique in this field. Current methods of three-dimensional reconstruction of two-dimensional images are based on the standard gray-scale imaging technique. However, precordial gray-scale data-set information is frequently of suboptimal quality because of data degradation caused by ultrasound attenuation by chest wall structures. This has limited the use of the transthoracic three-dimensional technique to “echogenic” patients. Doppler myocardial imaging (DMI), a new ultrasound technique based on the Doppler principle, is influenced less by chest wall attenuation and in addition offers a better boundary detection algorithm for the cardiac structures. To determine if there may be a potential benefit of DMI to acquire data for three-dimensional reconstruction, a 33-year-old woman with a large intracardiac mass was studied. In this case three-dimensional gray-scale and DMI data sets were compared and contrasted with pathologic information. DMI allowed both the quantification of mass volume and the correct definition of the morphology of the mass. It was also possible to identify the precise site of attachment of the mass to the mitral valve leaflets. The information thus obtained was correlated with both operative and pathologic findings.     

Synaptophysin expression on circulating tumor cells in patients with castration resistant prostate cancer undergoing treatment with abiraterone acetate or enzalutamide

Background

With the advent of secondary androgen receptor (AR)-targeted therapies in metastatic castration resistant prostate cancer (PC), nonadenocarcinoma PCs are becoming more prevalent. Many of these cancers express neuroendocrine markers, which may provide biomarkers for emergence of this disease state. We aimed to quantify the expression of synaptophysin (Syp) on circulating tumor cells (CTCs) from serial samples of patients being treated with abiraterone acetate or enzalutamide.

Safety of Gastric Resections During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis

Background  Cytoreductive surgery (CRS) including gastric resection combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the prognosis of selected patients with peritoneal surface malignancies. Perioperative morbidity of this aggressive treatment strategy is high; however, overall mortality can be low in specialized centers. The aim of this study was to assess the safety of gastric resections with anastomosis during CRS and HIPEC. Methods  Between 2005 and 2008, 204 patients underwent CRS and HIPEC at our tertiary referral centre. Of these, 37 procedures (male/female 24/13, median age 55 years) included gastric resections. The clinical data of all patients were introduced into a database and analyzed with respect to the morbidity associated with the gastric resections. Results  Of all patients included, 16 had pseudomyxoma peritonei, 11 gastric carcinoma, 4 ovarian carcinoma, 3 malignant peritoneal mesothelioma, and 3 colon carcinoma. Twenty-seven patients had previous surgery (n = 22) and/or systemic chemotherapy (n = 18). Fifteen total gastrectomies, 3 subtotal gastrectomies, 12 distal gastrectomies, and 7 gastric wedge resections were performed during CRS. The overall postoperative morbidity was 45%; main surgical complications were pancreatitis (n = 6), abdominal abscess (n = 4), bile leakage (n = 2), and digestive fistula (leakage of ileorectostomy and small bowel perforation) (n = 2). However, no complications occurred at the site of the esophageal anastomosis (n = 15), gastric anastomosis (n = 15) or gastric suture (n = 7). No patient died postoperatively during the hospitalization period. Conclusions  CRS in combination with HIPEC is associated with high postoperative morbidity; however, anastomosis following total or subtotal gastrectomy is safe in experienced centers. No leakages related to gastric resections occurred in this high-risk patient group. Pompiliu Piso and Przemyslaw Slowik have contributed equally to this study.     

A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo

BACKGROUND: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.     

Amphetamine and mCPP Effects on Dopamine and Serotonin Striatalin vivo Microdialysates in an Animal Model of Hyperactivity

In the neonatally 6-hydroxydopamine (6-OHDA)-lesioned rat hyperlocomotor activity, first described in the 1970s, was subsequently found to be increased by an additional lesion with 5,7-dihydroxytryptamine (5,7-DHT) (i.c.v.) in adulthood. The latter animal model (i.e., 134 microg 6-OHDA at 3 d postbirth plus 71 microg 5,7-DHT at 10 weeks; desipramine pretreatments) was used in this study, in an attempt to attribute hyperlocomotor attenuation by D,L-amphetamine sulfate (AMPH) and m-chlorophenylpiperazine di HCl (mCPP), to specific changes in extraneuronal (i.e., in vivo microdialysate) levels of dopamine (DA) and/or serotonin (5-HT). Despite the 98-99% reduction in striatal tissue content of DA, the baseline striatal microdialysate level of DA was reduced by 50% or less at 14 weeks, versus the intact control group. When challenged with AMPH (0.5 mg/kg), the microdialysate level of DA went either unchanged or was slightly reduced over the next 180 min (i.e., 20 min sampling), while in the vehicle group and 5,7-DHT (alone) lesioned group, the microdialysate level was maximally elevated by approximately 225% and approximately 450%, respectively--and over a span of nearly 2 h. Acute challenge with mCPP (1 mg/kg salt form) had little effect on microdialysate levels of DA, DOPAC and 5-HT. Moreover, there was no consistent change in the microdialysate levels of DA, DOPAC, and 5-HT between intact, 5-HT-lesioned rats, and DA-lesioned rats which might reasonably account for an attenuation of hyperlocomotor activity. These findings indicate that there are other important neurochemical changes produced by AMPH- and mCPP-attenuated hyperlocomotor activity, or perhaps a different brain region or multiple brain regional effects are involved in AMPH and mCPP behavioral actions.     

Modeling tardive dyskinesia: Predictive 5-HT2C receptor antagonist treatment

Tardive dyskinesia (TD), a movement disorder produced by long-term treatment with a classical antipsychotic drug, is generally considered to be a disorder of dopamine (DA) systems, since classical antipsychotics are potent DA D(2) receptor blockers. Also, acute DA D(1) agonist treatment of rats is known to produce vacuous chewing movements (VCMs), a behavioral feature resembling the oral dyskinesia that is so prominent in most instances of TD. In this paper we outline a series of studies in a new animal model of TD in which DA D(1) receptor supersensitivity was produced by neonatal 6-hydroxydopamine (6-OHDA) -induced destruction of nigrostriatal DA fibers. In rats so-lesioned 5-HT receptor supersensitivity is additionally produced, and in fact 5-HT receptor antagonists attenuate enhanced DA D(1) induction of VCMs. Moreover, in 6-OHDA-lesioned rats treated with haloperidol for one year, there a 2-fold increase in numbers of VCMs (vs intact rats treated with haloperidol); and this high frequency of VCMs persists for more than 6 months after discontinuing haloperidol treatment. During this stage, 5-HT(2) receptor antagonists, but not DA D(1) receptor antagonists, attenuate the incidence of VCMs. This series of findings implicates the 5-HT neuronal phenotype in TD, and promotes 5-HT(2) receptor antagonists, more specifically 5-HT(2C) receptor antagonists, as a rational treatment approach for TD in humans.