High‐resolution MALDI‐FT‐ICR MS imaging for the analysis of metabolites from formalin‐fixed,paraffin‐embedded clinical tissue samples

We present the first analytical approach to demonstrate the in situ imaging of metabolites from formalin‐fixed, paraffin‐embedded (FFPE) human tissue samples. Using high‐resolution matrix‐assisted laser desorption/ionization Fourier‐transform ion cyclotron resonance mass spectrometry imaging (MALDI‐FT‐ICR MSI), we conducted a proof‐of‐principle experiment comparing metabolite measurements from FFPE and fresh frozen tissue sections, and found an overlap of 72% amongst 1700 m/z species. In particular, we observed conservation of biomedically relevant information at the metabolite level in FFPE tissues. In biomedical applications, we analysed tissues from 350 different cancer patients and were able to discriminate between normal and tumour tissues, and different tumours from the same organ, and found an independent prognostic factor for patient survival. This study demonstrates the ability to measure metabolites in FFPE tissues using MALDI‐FT‐ICR MSI, which can then be assigned to histology and clinical parameters. Our approach is a major technical, histochemical, and clinicopathological advance that highlights the potential for investigating diseases in archived FFPE tissues. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Liver volume measurement: reason of the difference between in vivo CT-volumetry and intraoperative ex vivo determination and how to cope it

Purpose

Volumetric assessment of the liver regularly yields discrepant results between pre- and intraoperatively determined volumes. Nevertheless, the main factor responsible for this discrepancy remains still unclear. The aim of this study was to systematically determine the difference between in vivo CT-volumetry and ex vivo volumetry in a pig animal model.

Material and Methods

Eleven pigs were studied. Liver density assessment, CT-volumetry and water displacement volumetry was performed after surgical removal of the complete liver. Known possible errors of volume determination like resection or segmentation borders were eliminated in this model. Regression analysis was performed and differences between CT-volumetry and water displacement determined.

Results

Median liver density was 1.07 g/ml. Regression analysis showed a high correlation of r² = 0.985 between CT-volumetry and water displacement. CTvolumetry was found to be 13% higher than water displacement volumetry (p < 0.0001).

Conclusion

In this study the only relevant factor leading to the difference between in vivo CT-volumetry and ex vivo water displacement volumetry seems to be blood perfusion of the liver. The systematic difference of 13 percent has to be taken in account when dealing with those measures.     

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive individuals

Objective

This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated.

Methods

Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day) for 24 - 48 weeks in one of four treatment arms: HIV-negative (A), HIV-positive without HAART (B) and HIV-positive on HAART (C). Patients within arm C were randomized to receive open label either a nucleoside containing (C1) or a nucleoside free HAART (C2).

Results

168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy) were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000). Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708). Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209).

Conclusions

Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.     

Urethral Venous Malformation: An Unusual Cause of Recurrent Post-Coital Gross Haematuria in Association with Haematospermia

Three cases of recurrent post-coital haematuria are described. Extensive protracted investigations pinpointed urethral varicosities as the likely cause. All patients were successfully treated with diathermy fulguration.     

Pattern of Fatal Injuries in Counter Terrorist Operations: An Innovative Analysis through Embalming Services

Background

Mortal remains of the soldiers killed in counter-terrorist operations in Kashmir valley are sent to their home after undergoing mandatory embalming.

Methods

Injuries on the mortal remains of the soldiers killed in counter terrorist operations between Jan 1999 to Dec 2006 were analysed with respect to the agent, mode of injury, age, rank structure, body parts involved, seasonal variations and changing trends. Fatalities consequent to enemy action across line of control and fatalities of Kargil war were also analysed for comparison. Statistical analysis was done using chi square test for difference in proportions.

Result

Over the study period, terrorist induced injuries accounted for 8.16 deaths per thousand troops deployed whereas enemy action from across the line of control accounted for 0.63 deaths per thousand. Terrorist induced fatalities peaked in 2001 and thereafter revealed a declining trend (‘p’ < 0.001). Fatalities due to enemy action across line of control declined to zero since 25 Nov 2003 consequent to effective ceasefire. Of the total fatalities, 89.5% were killed in action (KIA) while 10.5% died of their wounds after reaching the hospital. Fatality to total injured ratio peaked to 29% in 2001 and than stabilized to about 23%. Mean KIA to total casualty ratio was 21%. The rank structure of the fatalities was officers 8.6%, JCOs 7.3%, and Other Ranks 84.1%. Most of the soldiers died young, 51% being below 25 years of age. Out of the terrorist induced fatalities, 78.2% died of gunshot wounds and 21.5% by splinters and improvised explosive devices (IED). The ratio was reversed in enemy induced fatalities and in Kargil war. Fatalities peaked during June to November and declined in winters. Body region wise, 23.4% of all deaths were due to head injury, 8.4% due to neck and maxillofacial injury, 18.4% due to injury to lungs and 11% due to heart injury. Most frequent target of the fatal bullet was brain (25.4%), closely followed by lungs (22.5%) and heart (12.3%). When soldier died of splinters / IED, multiple body parts were injured in 57.5%, brain in 17.3%, face & neck in 3.5%, heart in 6.6%, lungs in 5.3%, abdomen in 3.5% and limbs in 5.8%. Fatality due to head and heart injury peaked in 2001, while multiple injuries peaked in 2000, declined in 2001 and peaked again in 2004 and 2005 (‘p’ < 0.001). In fatalities of Kargil war, chest injuries were less but multiple injuries were more.

Conclusion

Most of the fatalities were due to gunshot wounds selectively aimed at head, face, neck and thorax. Therefore, a lightweight flexible and effective bulletproof protection for this area will conserve manpower.Key Words: Fatal injuries, Counter terrorist operations, Combat medical statistics     

Early and late components of error monitoring in violent offenders with psychopathy

BACKGROUND: One of the most recognizable features of psychopathy is the reduced ability to successfully learn and adapt overt behavior. This might be due to deficient processing of error information indicating the need to adapt controlled behavior. METHODS: Event-related potentials (ERPs) and behavioral components of error-monitoring processes were investigated in 16 individuals with psychopathy and in 18 healthy subjects. A letter version of the Eriksen flanker task was used in two conditions. The first condition (normal condition) required participants to press one of two buttons depending on the identity of the target stimulus. The second condition (signaling condition) required them to signal each time they had committed an error by making a second press on a signaling button. Early stages of error monitoring were investigated by using the error-related negativity (ERN/Ne) and post-error slowing as indexes. Later stages were explored by examining the error positivity (Pe) and signaling rates. RESULTS: Both groups showed similar ERN amplitudes and amounts of post-error slowing. The psychopathic group exhibited both reduced Pe amplitudes and diminished error-signaling rates compared with the control group. CONCLUSIONS: Individuals with psychopathy show intact early error processing and automatic behavioral adaptation but have deficits in later stages of error processing and controlled behavioral adaptation. This is an indication that individuals with psychopathy are unable to effectively use error information to change their behavior adequately.