Pro-inflammatory type-1 and anti-inflammatory type-2 macrophages differentially modulate cell survival and invasion of human bladder carcinoma T24 cells

Findings from numerous studies suggest that inflammation is likely to have an important role in bladder carcinogenesis and cancer disease progression. While macrophages (M?s) constitute a major inflammatory component of the stroma of human bladder carcinoma, the regulatory role of such inflammatory leukocytes in tumor cell survival and invasion remains elusive. Human urothelial bladder cancer (UBC) T24 cells and monocyte-derived macrophages were used to study the relative contribution of pro-inflammatory type-1 (M?-1) and anti-inflammatory type-2 (M?-2) macrophages in the regulation of UBC cell behaviour. Cell-to-cell studies indicated that the number of viable cells were considerable higher in T24 cell/M?-2 cocultures but lower in T24 cell/M?-1 cocultures when compared to cultures of T24 cells alone. M?-1-derived factors inhibit T24 cell growth but fail to induce caspase-3-mediated apoptosis. M?-2-derived factors have the ability to suppress the inhibitory effect of M?-1-derived factors on T24 cell growth. Exogenous interleukin (IL)-10 reverse M?-1-mediated arrest growth in T24 cell/M?-1 cell cocultures. Further analyses showed that M?-1-derived factors induced tumor necrosis factor (TNF)-α gene expression, promoted cellular invasiveness and increased phosphoinositide 3-kinase (PI 3-K)/Akt signaling pathway activity in T24 cells. Inhibition of PI 3-K activation in T24 cells or blockade of TNFα receptor in T24 cell/M?-1 cell cocultures decreased cellular invasiveness but did not affect T24 cell viability. Based on these observations, we propose that similar functional interactions between UBC cells and infiltrating macrophages can take place in vivo and influence tumor cell survival and invasion during bladder cancer progression.     

Nonlinear hemodynamic responses in human epilepsy: a multimodal analysis with fNIRS-EEG and fMRI-EEG

Functional magnetic resonance imaging (fMRI) combined with electroencephalography (fMRI-EEG) is a neuroimaging technique based on the blood oxygenation level dependent (BOLD) signal which has been shown to be useful in the study of epilepsy for the localization of the epileptogenic focus. Functional near-infrared spectroscopy (fNIRS) combined with EEG (fNIRS-EEG) is another imaging technique based on the measurement of oxygenated and deoxygenated hemoglobin with complementary clinical potential in epilepsy, for continuous patient monitoring, language lateralization, and focus localization.In this work fMRI-EEG and fNIRS-EEG are used to quantify nonlinear hemodynamic responses in three cases of human refractory focal epilepsy, by using the Volterra kernel expansion up to second order. Prior to analyzing real data, extensive simulations are carried out to show that nonlinearities are estimable. The Volterra methodology is then applied to multimodal data recorded from 3 epileptic patients selected for their frequent spiking activity. Care is taken to account for variability of hemodynamic responses due to other causes than Volterra nonlinearities. Statistically significant nonlinearities are observed for all patients and all modalities. Good concordance between fNIRS and fMRI is found for both the amplitude of the Volterra responses, and, with limitations, in the localization of the epileptic focus and regions of inverted responses (negative BOLD signals). In one patient, Volterra nonlinearities allowed epileptic focus identification with fMRI, while analyses without nonlinearities failed to see it. In simulations when nonlinearities were included, analysis without Volterra nonlinearities performed poorly. These two observations suggest routinely checking for nonlinearities in functional imaging of patients presenting with frequent spikes.     

Liver transplantation in Indian Armed Forces—initial experience

Background

This study retrospectively analyses the initial experience of liver transplantation (LT) in the Indian Armed Forces.

Methods

Fifty-three patients underwent LT at Army Hospital (R&R) Delhi Cantt. between March 2007 and March 2011. Of these 35 patients underwent deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) was carried out in 18 patients. The surgical techniques, complications and mortality were analysed.

Results

A high consent rate of 35.9% for organ donation was achieved by the Armed Forces Organ Retrieval and Transplantation Authority (AORTA). Biliary complications occurred in five patients (9.4%). However, most of them could be managed by endoscopic interventions. Hepatic artery thrombosis (HAT) occurred in five patients (9.4%). Of these, two DDLT grafts were revascularised following HAT, by creating extra-anatomic arterial conduits with excellent outcome. The overall mortality was 18.8% (n = 10). There was no significant difference in the overall complications or mortality in patients undergoing DDLT or LDLT.

Conclusion

The overall survival and morbidity in this study is comparable to those from other centres. Urgent revascularisation of grafts following HAT should be attempted as it can salvage grafts with satisfactory outcome. There is a reduction in the incidence of biliary complications with refinements in surgical techniques.     

Multichannel wearable system dedicated for simultaneous electroencephalography∕near-infrared spectroscopy real-time data acquisitions

Functional neuroimaging is becoming a valuable tool in cognitive research and clinical applications. The clinical context brings specific constraints that include the requirement of a high channel count to cover the whole head, high sensitivity for single event detection, and portability for long-term bedside monitoring. For epilepsy and stroke monitoring, the combination of electroencephalography (EEG) and functional near-infrared spectroscopy (NIRS) is expected to provide useful clinical information, and efforts have been deployed to create prototypes able to simultaneously acquire both measurement modalities. However, to the best of our knowledge, existing systems lack portability, NIRS sensitivity, or have low channel count. We present a battery-powered, portable system with potentially up to 32 EEG channels, 32 NIRS light sources, and 32 detectors. Avalanche photodiodes allow for high NIRS sensitivity and the autonomy of the system is over 24 h. A reduced channel count prototype with 8 EEG channels, 8 sources, and 8 detectors was tested on phantoms. Further validation was done on five healthy adults using a visual stimulation protocol to detect local hemodynamic changes and visually evoked potentials. Results show good concordance with literature regarding functional activations and suggest sufficient performance for clinical use, provided some minor adjustments were made.     

Missile Injuries of Brain – an Experience in Northern Sector

During a period of one year, from Jan 99 to Dec 99, 60 cases of missile injuries were treated at our centre. 59 were males and one was a female and their average age was 25 years. 43 patients had suffered splinter injuries, 12 had gunshot wounds and 5 had suffered injuries by improvised explosive devices. Glasgow coma scale was < 5 in 8 patients, 5–8 in 14, 8–12 in 30 and 13–15 in 8 patients. Extensive comminution of skull bones was found in 10 patients. 35 patients had more or less clear penetration of the skull and the rest had orbito-cranial or facio-cranial wounds. CT scan revealed small haemorrhagic contusion with in-driven bones without mass effect in 15, contusion with mass effect in 36 cases, cortical contusions without in driven bones (tangential injuries) in 3, distant intracranial contusions in 4, intraventricular haemorrhages in 5, multilobar injuries in 14, and unilobar injury in 40. 52 patients were operated upon at our centre of which 30 were operated within 24 hours, 10 between 24 to 48 hours, 12 between 48–72 hours. Six patients were treated conservatively and 2 required only simple closure of scalp wound. Craniectomy was done in 10 and craniotomy in 42 patients. Two patients developed wound sepsis, one each developed aspiration pneumonia, septicemia, deep vein thrombosis and post-traumatic hydrocephalus. On follow up at 6 months, outcome as per Glasgow outcome scale was as follows: good outcome – 42, moderate disability in 7, severe disability in 6 and death in 5 patients. Retained bone fragments were found in 40% on follow up CT scan but none had brain abscess.Key Words: Brain, Craniotomy, Favourable outcome, Less aggressive surgery, Missile injury