ENDOSCOPIC ULTRASOUND GUIDED TRUCUT BIOPSY

Endoscopic ultrasound (EUS) is sensitive for staging gastrointestinal malignancies and pancreatic lesions. EUS‐fine‐needle aspiration (EUS‐FNA) offers a diagnostic accuracy of about 60–90% for pancreatic tumors and > 90% for lymph nodes. There are several limitations of EUS‐FNA including the need for on‐site cytopathology review. In addition, accuracy of cytologic review is hampered by the presence of blood, benign epithelial cells, desmoplasia, and well‐differentiated tumors. Furthermore, the small biopsy sample and destruction of tissue architecture limits the diagnostic sensitivity for GISTs and lymphomas. Many of these problems can be overcome with use of EUS trucut biopsy (TCB) needles. These large caliber, cutting needles acquire larger tissue samples allowing preservation of tissue architecture and histologic examination. Our recently described experience with EUS‐TCB initially in swine and later humans demonstrated the safety for acquiring histologic tissue representative of the target organs sampled enabling accurate diagnosis. These studies suggested greater diagnostic accuracy of EUS‐TCB for submucosal mass lesions and lymphoma and potentially the need for fewer needle passes for solid pancreatic neoplasms. In this paper we will review the current TCB literature, device design and technique, help troubleshoot potential problems, and offer opinion as to the utility and role of this new device.     

Nkx2.5‐negative myocardium of the posterior heart field and its correlation with podoplanin expression in cells from the developing cardiac pacemaking and conduction system

Recent advances in the study of cardiac development have shown the relevance of addition of myocardium to the primary myocardial heart tube. In wild‐type mouse embryos (E9.5–15.5), we have studied the myocardium at the venous pole of the heart using immunohistochemistry and 3D reconstructions of expression patterns of MLC‐2a, Nkx2.5, and podoplanin, a novel coelomic and myocardial marker. Podoplanin‐positive coelomic epithelium was continuous with adjacent podoplanin‐ and MLC‐2a‐positive myocardium that formed a conspicuous band along the left cardinal vein extending through the base of the atrial septum to the posterior myocardium of the atrioventricular canal, the atrioventricular nodal region, and the His‐Purkinje system. Later on, podoplanin expression was also found in the myocardium surrounding the pulmonary vein. On the right side, podoplanin‐positive cells were seen along the right cardinal vein, which during development persisted in the sinoatrial node and part of the venous valves. In the MLC‐2a‐ and podoplanin‐positive myocardium, Nkx2.5 expression was absent in the sinoatrial node and the wall of the cardinal veins. There was a mosaic positivity in the wall of the common pulmonary vein and the atrioventricular conduction system as opposed to the overall Nkx2.5 expression seen in the chamber myocardium. We conclude that we have found podoplanin as a marker that links a novel Nkx2.5‐negative sinus venosus myocardial area, which we refer to as the posterior heart field, with the cardiac conduction system. Anat Rec, 290:115–122, 2007. © 2006 Wiley‐Liss, Inc.     

Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies

Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration-dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process.     

On the Shift from Anticipatory Heart Rate Deceleration to Acceleratory Recovery: Revisiting the Role of Response Factors

The influence of inducing motor responses of low and high force at different times in the cardiac cycle was examined. A handgrip response was used which allowed the separation of response initiation from response completion. Based on earlier work, we expected initiation, rather than completion, to initiate poststimulus cardiac acceleration. We also thought that preparation for a high force response might alter preparatory changes of interbeat interval differently from preparation for a low force response. Fifteen college-aged male subjects performed a warned reaction time task in which a visual stimulus signalled a handgrip requiring either a high or a low force to close. NoGo trials in which an inhibit signal was presented occurred on 12% of the trials. Stimuli occurred either on the R-wave of the electrocardiogram or 300 ms later. Reaction speed was varied in different trial blocks by rewarding response times of 200 ms (+/- 50 ms), 300 ms, or 400 ms. Results based on the timing of response initiation were essentially identical to those based on the timing of response completion. High force relative to low force was associated with both earlier response initiation and earlier cardiac acceleration. Force did not alter preparatory cardiac deceleration. Force and response speed did, however, alter the level of heart rate after response occurrence. Thus, response initiation (or an earlier response process) appears to induce a cardiac acceleration whose level is influenced by the speed and force of the motor response.     

Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness

OBJECTIVE: Major depression is associated with defective antioxidant defenses. Vitamin E is the major fat soluble antioxidant in the body. The aim of the present study is to examine serum vitamin E concentrations in major depressed patients versus normal volunteers. METHOD: Serum vitamin E concentrations were measured in 26 healthy volunteers and 42 major depressed patients by means of HPLC. Since vitamin E is a fat soluble vitamin, and serum vitamin E concentrations are strongly related to these of low-density-lipoprotein cholesterol (LDL-C) and triglycerides, we have adjusted the results for possible differences in these lipids. The numbers of peripheral blood leukocytes were measured. RESULTS: Patients with major depression had significantly lower serum vitamin E concentrations than healthy controls. The area under the ROC (receiver operating characteristics) curve was 83%. There were significant and negative correlations between serum vitamin E and number of total leukocytes and neutrophils. CONCLUSIONS: Major depression is accompanied by significantly lower serum vitamin E concentrations, suggesting lower antioxidant defenses against lipid peroxidation. The results could, in part, explain previous findings, which suggest increased lipid peroxidation in major depression.     

Identification and characterization of human pulmonary dendritic cells

Dendritic cells (DC) are specialized antigen-presenting cells, linking innate and adaptive immune responses, and thus play an important role in immunologically mediated diseases, including pulmonary diseases such as asthma and respiratory viral infections. Although much is known about the characteristics of lung DC in animal models, very few data concerning human lung DC are available. The goal of our study was to identify and characterize dendritic cells in human lung by preparing single-cell suspensions from surgical resection specimens and subsequent labeling with the recently developed blood dendritic cell antigen (BDCA) markers. A straightforward isolation procedure was developed to avoid phenotypical and functional changes induced by extensive purification methods. In this way, human lung DC were directly identified without the need for an additional adherence step for further purification. For the first time, we demonstrate the presence of three previously unidentified DC subsets in human lung digests: myeloid DC type 1 (BDCA1+/HLA-DR+), myeloid DC type 2 (BDCA3+/HLA-DR+), and plasmacytoid DC (BDCA2+/CD123+). The presence of CD1a+ DC in the human lung was confirmed. The identification and characterization of different human pulmonary DC subtypes is of great importance for the future development of DC-based immunotherapies.     

Full-thickness macular holes treated with vitrectomy and tissue glue

In the surgical treatment of full-thickness macular holes good results have been published with the combination of vitrectomy, gas and application of Transforming Growth Factor 2. Other authors report a 73% success rate in closing a full-thickness macular hole after vitrectomy and gas tamponade alone. We used, in addition to vitrectomy and gas tamponade, a tissue glue to stimulate adhesion of the elevated cuff of neurosensory retina surrounding a full-thickness macular hole and to close to hole itself. A total of 15 eyes of 13 patients (3 men, 10 women), with stage 3 and 4 macular holes were operated. All of the 13 uncomplicated cases showed complete closure of the macular hole. In one case (8%) the visual acuity decreased one line in spite of a funduscopically closed hole, and in two cases (16%) visual acuity remained the same despite closure. Increased visual acuity was seen in ten cases (76%), eight of which improved more than two lines.     

Effect of bronchodilation on regional lung function measured by 133Xe and gamma camera

Using ¹³³Xe, a gamma camera and off-line data handling the effect of inhaled Salbutamol on regional lung function was measured in six patients with chronic obstructive lung disease and associated bronchospasm.After bronchodilation only minor changes were obtained in regional ventilation or in the arterial hypoxemia, although the overall airways obstruction improved markedly. These findings suggest that the bronchodilating agent had an effect mainly on the larger airways and almost did not influence the function of the more peripheral lung units responsible for gas exchange. Also, a slight but direct effect on the perfusion was demonstrated. The effect on the ¹³³Xe ventilation-perfusion ratio was not correlated with that on the hypoxemia, indicating that the first is not a good representation of the latter.Supported by a grant from the Fonds voor Geneeskundig Wetenschappelijk Onderzoek     

Benefit of combined resynchronization and defibrillator therapy in heart failure patients with and without ventricular arrhythmias.

OBJECTIVES: We attempted to assess the efficacy of combined cardiac resynchronization therapy-implantable cardioverter-defibrillator (CRT-ICD) in heart failure patients with and without ventricular arrhythmias. BACKGROUND: Because CRT and ICDs both lower all-cause mortality in patients with advanced heart failure, combination of both therapies in a single device is challenging. METHODS: A total of 191 consecutive patients with advanced heart failure, left ventricular ejection fraction <35%, and a QRS duration >120 ms received CRT-ICD. Seventy-one patients had a history of ventricular arrhythmias (secondary prevention); 120 patients did not have prior ventricular arrhythmias (primary prevention). During follow-up, ICD therapy rate, clinical improvement after 6 months, and mortality rate were evaluated. RESULTS: During follow-up (18 +/- 4 months), primary prevention patients experienced less appropriate ICD therapies than secondary prevention patients (21% vs. 35%, p < 0.05). Multivariate analysis revealed, however, no predictors of ICD therapy. Furthermore, a similar, significant, improvement in clinical parameters was observed at 6 months in both groups. Also, the mortality rate in the primary prevention group was lower than in the secondary prevention group (3% vs. 18%, p < 0.05). CONCLUSIONS: As 21% of the primary prevention patients and 35% of the secondary prevention patients experienced appropriate ICD therapy within 2 years after implant, and no predictors of ICD therapy could be identified, implantation of a CRT-ICD device should be considered in all patients eligible for CRT.