Tru-Cut biopsy of mediastinal masses guided by real-time sonography

Twenty-five patients with mediastinal masses, arising in the anterior, middle and posterior mediastinum but in contact with the chest wall, underwent ultrasound (US) guided biopsy with a Tru-Cut needle to obtain a core biopsy specimen from the mass. In all these patients adequate tissue was obtained for a histopathological diagnosis and no major complications were observed. The advantage of core biopsy over fine needle aspiration cytology in mediastinal masses is that accurate histopathological differentiation, and classification of carcinomas and lymphomas is possible. The advantage of performing real-time US guided biopsy is that puncture of the lung and mediastinal vascular structures is avoided.     

Dissociation of the ventilatory and lactate thresholds following caffeine ingestion

Caffeine ingestion prior to the start of exercise has been shown to have an effect on ventilatory parameters and substrate utilization. Changes in either substrate utilization or ventilatory parameters may influence the determination of the lactate threshold (LT) and/or the ventilatory threshold (VT). Therefore, it was the purpose of this investigation to determine whether the VT and LT occur at similar metabolic rates and what effect caffeine ingestion will have on these two measures. Ten male subjects completed two maximal exercise bouts on the treadmill using a single blind procedure. One trial was performed 45 min after the ingestion of caffeine citrate (CC) in an amount equal to 7.0 mg of anhydrous caffeine.kg-1 body weight. The second trial was performed 45 min after the ingestion of a gelatin powdered placebo (P). Ventilatory parameters were monitored on a breath-by-breath basis, and blood for lactate determination was obtained from an antecubital vein every minute. Maximal oxygen consumption did not differ significantly between the CC (60.3 +/- 5.2 ml.kg-1.min-1) and P (59.7 +/- 5.6 ml.kg-1.min-1) trials. Oxygen consumption (VO2) values during the P trial at the VT (40.2 +/- 6.1 ml.kg-1.min-1) and the LT (38.6 +/- 3.3 ml.kg-1.min-1) were not significantly different (P less than 0.05). During the CC trial, VO2 values at the VT (44.4 +/- 6.6 ml.kg-1.min-1) and the LT (39.7 +/- 5.8 ml.kg-1.min-1) were significantly different. When comparing the VO2 at the LTs between the CC and P trials, there was no significant difference. There was, however, a significant difference in VO2 at the VTs when comparing the two trials. These data demonstrate a dissociation between the VT and LT following caffeine ingestion and suggest that the use of the VT as an indicator of the LT may be inappropriate following ingestion of moderate dosages of caffeine.     

The effectiveness of polyethylene versus titanium particles in inducing osteolysis in vivo.

Bearing surface wear and periprosthetic osteolysis due to wear particles are among the most common reasons for joint replacement failure. A murine calvarial model of wear particle-induced osteolysis has been used to identify different biologic factors associated with this problem and to test nonsurgical methods of modulating the host response to particulate debris. This model has utilized titanium particles, however, in clinical practice the most common source of particulate debris is polyethylene particles from bearing surface wear. We now report a calvarial model of wear particle-induced osteolysis based on commercially available polyethylene particles. We found that compared to sham surgery osteoclast recruitment and bone resorption can be induced by introduction of the titanium particles or polyethylene particles. However, bone resorption was significantly higher with polyethylene particles compared to titanium particles (p=0.02). We consider the polyethylene based murine calvarial model of wear particle-induced osteolysis a reliable and clinically relevant tool to understand the host factors and potential pharmacologic interventions that can influence wear debris generated osteolysis. This model might serve as an extension of the well-established titanium based bone resorption model.     

Osteopontin is a negative regulator of proliferation and differentiation in MC3T3-E1 pre-osteoblastic cells

Osteopontin (OPN) is an important mediator of bone remodeling. However, the role of OPN in the process of bone formation is not fully understood. In previous studies, we have shown that MC3T3-E1 pre-osteoblastic cells at higher passage number exhibited weakened osteogenic capacity and elevated OPN mRNA expression. In this work, we investigated the role of OPN on proliferation and differentiation of low-passage MC3T3-E1 cells by studying stable cell lines overexpressing either OPN mRNA or its antisense RNA. Overexpression was verified by both Northern and Western blot analyses. Overexpression of OPN markedly inhibited proliferation as determined by daily cell counts, while overexpression of antisense RNA stimulated cellular proliferation. We also examined the effect of OPN level on BMP-2-induced alkaline phosphatase activity. Overexpression of OPN inhibited BMP-2 responsiveness while overexpression of antisense RNA enhanced the effect of BMP-2 on alkaline phosphatase activity. Increased OPN expression also caused decreases in expression of osteocalcin and bone sialoproteins while a reduction of OPN level caused the opposite. Furthermore, endogenous OPN expression in response to BMP-2 exhibited a biphasic pattern, that is, it was initially inhibited and then enhanced by the treatment of BMP-2, indicating that OPN might function as a negative feedback regulator for osteoblastic differentiation. Finally, overexpression of OPN inhibited mineral deposition. In contrast, overexpression of antisense RNA enhanced mineral deposition. These results indicate that OPN is a negative regulator of proliferation and differentiation in MC3T3-E1 cells.     

Biochemical alterations associated with ALS

Our objective was to identify metabolic pathways affected by ALS using non-targeted metabolomics in plasma, comparing samples from healthy volunteers to those from ALS patients. This discovery could become the basis for the identification of therapeutic targets and diagnostic biomarkers of ALS. Two distinct cross-sectional studies were conducted. Plasma was collected from 62 (Study 1) and 99 (Study 2) participants meeting El Escorial criteria for possible, probable, or definite ALS; 69 (Study 1) and 48 (Study 2) healthy controls samples were collected. Global metabolic profiling was used to detect and evaluate biochemical signatures of ALS. Twenty-three metabolites were significantly altered in plasma from ALS patients in both studies. These metabolites include biochemicals in pathways associated with neuronal change, hypermetabolism, oxidative damage, and mitochondrial dysfunction, all of which are proposed disease mechanisms in ALS. The data also suggest possible hepatic dysfunction associated with ALS. In conclusion, the data presented here provide insight into the pathophysiology of ALS while suggesting promising areas of focus for future studies. The metabolomics approach can generate novel hypotheses regarding ALS disease mechanisms with the potential to identify therapeutic targets and novel diagnostic biomarkers.     

Cardiac paraganglioma: diagnostic and surgical challenges

Primary cardiac paragangliomas are rare extra-adrenal tumors. Though they account for less than 1% of all primary cardiac tumors, they are considerable sources of morbidity and mortality. In this case review, we discuss the challenges associated with the diagnosis and management of cardiac paragangliomas.