Intracranial mycotic aneurysm due to Aspergillus species.

BACKGROUND: Intracranial true mycotic aneurysms are uncommon and usually fatal. We report two patients with basilar mycotic aneurysms due to Aspergillus species following surgical interventions. Both patients had subarachnoid hemorrhage and diagnosis was made at autopsy only. The literature regarding etiology, clinical presentation, predisposing conditions and outcome of intracranial true mycotic aneurysms is reviewed from 1990-2005. A high index of clinical suspicion with prompt diagnosis and early treatment may improve patient outcome.     

Gastrointestinal dysfunction in Parkinson’s disease: molecular pathology and implications of gut microbiome,probiotics, and fecal microbiota transplantation

Journal of Neurology - Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as...     

Outcome of percutaneous continuous drainage of psoas abscess: A clinically guided technique

Background:

Percutaneous aspiration of abscesses under ultrasonography (USG) and computer tomography (CT) scan has been well described. With recurrence rate reported as high as 66%. The open drainage and percutaneous continuous drainage (PCD) has reduced the recurrence rate. The disadvantage of PCD under CT is radiation hazard and problems of asepsis. Hence a technique of clinically guided percutaneous continuous drainage of the psoas abscess without real-time imaging overcomes these problems. We describe clinically guided PCD of psoas abscess and its outcome.

Materials and Methods:

Twenty-nine patients with dorsolumbar spondylodiscitis without gross neural deficit with psoas abscess of size >5 cm were selected for PCD. It was done as a day care procedure under local anesthesia. Sequentially, aspiration followed by guide pin-guided trocar and catheter insertion was done without image guidance. Culture sensitivity was done and chemotherapy initiated and catheter kept till the drainage was <10 ml for 48 hours. Outcome assessment was done with relief of pain, successful abscess drainage and ODI (Oswestry Disability Index) score at 2 years.

Results:

PCD was successful in all cases. Back and radicular pain improved in all cases. Average procedure time was 24.30 minutes, drain output was 234.40 ml, and the drainage duration was 7.90 days. One patient required surgical stabilisation due to progression of the spondylodiscitis resulting in instability inspite of successful drainage of abscess. Problems with the procedure were noticed in six patients. Multiple attempts (n = 2), persistent discharge (n = 1) for 2 weeks, blocked catheter (n = 2) and catheter pull out (n = 1) occurred with no effect on the outcome. The average ODI score improved from 62.47 to 5.51 at 2 years.

Conclusions:

Clinically guided PCD is an efficient, safe and easy procedure in drainage of psoas abscess.     

A temperature-dependent switching of the exchange bias effect from negative to positive under a fixed intermediate cooling field

An interfacial coupling origin of the exchange bias effect (EBE) is a novel phenomenon due to its technological and fundamental importance. We have carefully synthesized an Fe₃O₄@NiO (FO@N) core@shell (CS) nanostructure using a co-precipitation method, and the CS nanostructure formation was evident from the HRTEM analysis. The magnetic measurement study endorses unique characteristics on the temperature-dependent EBE switching from negative to the positive axis under a fixed cooling field. To the best of our knowledge, this unique characteristic behavior at a fixed cooling field has not been reported, particularly for the ferro/ferrimagnetic@antiferromagnetic FiM@AFM CS nanostructure. The switching is attributed to a formation of ferromagnetic (negative) or antiferromagnetic (positive) coupling arrangement at the magnetically disordered interface of two materials.

An interfacial coupling origin of the exchange bias effect (EBE) is a novel phenomenon due to its technological and fundamental importance.     

Emerging trends in the pharmacotherapy of chronic pain

The pharmacotherapy for pain is dominated by conventional analgesics such as the opioids and the non-steroidal anti-inflammatory drugs. Recent advances in the understanding of the mechanisms of pain in general and chronic pain in particular, opened the field of analgesic therapy to newer pharmacological targets, which are aimed at improved efficacy and enhanced tolerability over conventional antipain treatments. Many novel targets are still in preclinical development, but some have made it into human trials and have shown promise. Newer anticonvulsants, new generation cyclooxygenase inhibitors, better tolerated glutamate modulators and balanced serotonin/noradrenaline re-uptake inhibitors are some targets that have shown promise in the clinic. These and other compounds that are in advanced phases of development for chronic pain are reviewed in this paper. It is hoped that the decade of pain control and research will lead us to an arsenal of effective and safe analgesics that will conquer the problem of chronic pain.     

Axl receptor tyrosine kinase is up-regulated in metformin resistant prostate cancer cells

Recent epidemiological studies showed that metformin, a widely used anti-diabetic drug might prevent certain cancers. Metformin also has an anti-proliferative effect in preclinical studies of both hematologic malignancies as well as solid cancers and clinical studies testing metformin as an anti-cancer drug are in progress. However, all cancer types do not respond to metformin with the same effectiveness or acquire resistance. To understand the mechanism of acquired resistance and possibly its mechanism of action as an anti-proliferative agent, we developed metformin resistant LNCaP prostate cancer cells. Metformin resistant LNCaP cells had an increased proliferation rate, increased migration and invasion ability as compared to the parental cells, and expressed markers of epithelial-mesenchymal transition (EMT). A detailed gene expression microarray comparing the resistant cells to the wild type cells revealed that Edil2, Ereg, Axl, Anax2, CD44 and Anax3 were the top up-regulated genes and calbindin 2 and TPTE (transmembrane phosphatase with tensin homology) and IGF1R were down regulated. We focused on Axl, a receptor tyrosine kinase that has been shown to be up regulated in several drug resistance cancers. Here, we show that the metformin resistant cell line as well as castrate resistant cell lines that over express Axl were more resistant to metformin, as well as to taxotere compared to androgen sensitive LNCaP and CWR22 cells that do not overexpress Axl. Forced overexpression of Axl in LNCaP cells decreased metformin and taxotere sensitivity and knockdown of Axl in resistant cells increased sensitivity to these drugs. Inhibition of Axl activity by R428, a small molecule Axl kinase inhibitor, sensitized metformin resistant cells that overexpressed Axl to metformin. Inhibitors of Axl may enhance tumor responses to metformin and other chemotherapy in cancers that over express Axl.     

Double parabolic Kirschner-wires as dynamic distractor for treatment of unstable intraarticular phalangeal fractures of hand

Background:

Treatment of complex injuries of interphalangeal joints (IPJs) is difficult. The restoration of joint stability for early joint mobility till fracture union is the key for successful outcome. Although various treatment options like dynamic splinting, external fixator, closed reduction, transarticular Kirschner (K)-wire and ORIF, etc., are available in literature, a universally accepted ideal treatment for complex intraarticular fractures of IPJs is still evolving. Open reduction is difficult because fixation of volar fragment is often impractical and radical procedures like volar plate arthroplasty, arthrodesis or joint replacement, etc., may become mandatory for salvage. We describe percutaneous technique to treat unstable fractures and dorsal fracture–dislocations of the PIP joint and report short-term postoperative results.

Materials and Methods:

Ten cases of unstable or potentially unstable intraarticular fractures including pilon fractures and fracture-dislocations of IP joints were treated percutaneously by double parabolic K-wire technique (DPK). The device was used as a dynamic distraction, using the principle of ligamentotaxis. The idea was to commence early postoperative continuous active and active-assisted joint motion exercises and to carry on the frame as a definitive treatment for achieving fracture union.

Results:

In all patients of fracture-dislocation the reduction was satisfactory and early mobility was achieved. Although there is a tendency towards over-distraction, no loss of reduction occurred. Pin tract infection occurred in one with no delayed union or nonunion. The average total range of motion for each involved IP joint was 93.5 degree and the average total active range of motion was 90.8° each at the end of 4 months followup. Excellent to good results were restored in nearly all cases without further interventions.

Conclusion:

DPK technique may be a cheap and valuable definitive treatment option in the management of unstable or potentially unstable intraarticular fractures of IPJs. The technique gave satisfactory radiological union and functional outcome in our small series. This technique may be worth considering in unstable or potentially unstable intraarticular fractures of IPJs with intact collateral ligaments and when other treatment options are impractical.     

Clinical experience with the use of clotting factor concentrates in oral anticoagulation reversal

We report the clinical experience of a large Haemophilia Centre and Haemostasis Unit in reversing oral anticoagulation (OAC) using clotting factor concentrates. This is a retro-spective study extending over 2 years (January 1996-December 1997). Reversal was per-formed using a combination of factor IX and factor VII concentrates administered by intravenous infusion, in a dose varying between 12 i.u./kg and 50 i.u./kg. We identified 20 episodes of OAC reversal in 18 patients, with a prevalence of 10 reversal episodes/1000 OAC patients/year. The median age was 77 years old (range 53-92 years). Indications for OAC reversal were divided into major bleeds (muscle haematoma [9], haematuria [3], subarachnoid haemorrhage [1], oesophageal bleeding [1], haemoptysis [1], haemarthrosis [1]); minor bleeds (extensive bruising [9], epistaxis [3], oral cavity bleeding [1]); and emergency invasive investigation (2). Pre-reversal, the international normalized ration (INR) was greater than 6.0 in 15/18 patients. Post-infusion, there was an immediate reduction in the INR towards normal (mean 1.3; range 1.1-2.3). There were no thrombotic complications or other adverse effects. The median use of factor 9 A concentrate was 2300 units/patient (range 570-4195), at a cost of à £645/patient and for factor VII concentrate 2200 units/patient (range 815-3630), at a cost of à £664/patient. Clotting factor concentrates provide a safe, rapid and effective means for OAC reversal and although expensive it is the treatment of choice in the over anticoagulated, bleeding patient.     

Rapid, simple influenza RNA extraction from nasopharyngeal samples

This report describes the development and pre-clinical testing of a new, random-access RNA sample preparation system (TruTip) for nasopharyngeal samples. The system is based on a monolithic, porous nucleic acid binding matrix embedded within an aerosol-resistant pipette tip and can be operated with single or multi-channel pipettors. Equivalent extraction efficiencies were obtained between automated QIAcube and manual TruTip methods at 10(6) gene copies influenza A per mL nasopharyngeal aspirate. Influenza A and B amended into nasopharyngeal swabs (in viral transport medium) were detected by real-time RT-PCR at approximately 745 and 370 gene copies per extraction, respectively. RNA extraction efficiency in nasopharyngeal swabs was also comparable to that obtained on an automated QIAcube instrument over a range of input concentrations; the correlation between threshold cycles (or nucleic acid recovery) for TruTip and QIAcube-purified RNA was R(2)>0.99. Preclinical testing of TruTip on blinded nasopharyngeal swab samples resulted in 98% detection accuracy relative to a clinically validated easyMAG extraction method. The physical properties of the TruTip binding matrix and ability to customize its shape and dimensions likewise make it amenable to automation and/or fluidic integration.