Severe acute pancreatitis in the early postoperative period due to afferent loop syndrome following gastrectomy for gastric cancer.

Afferent loop syndrome (ALS) is an uncommon complication of gastrojejunostomy. It may be acute or chronic depending on whether symptoms manifest within 7 days of surgery. Rarely acute ALS may give rise to acute pancreatitis. It may present early in the postoperative course and, if diagnosed late, may result in organ failure within 48h. We report a middle-aged woman with carcinoma of the stomach managed by subtotal gastrectomy with Billroth II gastrojejunostomy and Braun jejunojejunostomy. The patient developed vomiting and abdominal pain in the first postoperative day with acute renal shutdown and about 500ml drain output of dirty fluid. On investigation, a diagnosis of acute pancreatitis due to afferent loop syndrome was made, and the patient was resuscitated in the intensive care unit. However, she showed early signs of organ failure and succumbed to her condition within 6 days of surgery. Since the complication is rare following gastrojejunostomy and often mimics ALS, an early diagnosis becomes difficult. If delay in management happens, premature organ failure may lead to high morbidity and mortality.

Factors impacting on technical success in stroke thrombectomy: experience of a UK neuro-interventional unit.

AIM: To investigate factors that could impact on recanalisation and reperfusion in patients undergoing mechanical thrombectomy and to assess the technical success over time. MATERIALS AND METHODS: Two hundred consecutive patients who underwent thrombectomy for a proximal anterior circulation occlusion were dichotomised into equal groups (groups 1 and 2) based on the date that immediate access to emergency general anaesthesia (GA) commenced. RESULTS: Recanalisation success using thrombolysis in cerebral infarction (TICI) 2b/3 or TICI 2c/3 significantly improved in group 2 (67% versus 93%, p<0.0001; 52% versus 78%, p=0.0002). Symptomatic haemorrhage also reduced from 9% to 4%. Despite similar presentation Alberta Stroke Program Early (computed tomography) CT Scores (ASPECTS), post-procedural ASPECTS was significantly increased in group 2 (7; [interquartile range {IQR} 4-9] versus 8 [IQR 7-9]; p=0.0034). The number of patients with a post procedural ASPECTS of 8-10 increased (46% versus 64%, p=0.0155) and the difference in ASPECTS between pre- and post-thrombectomy CT was significantly lower (2 [IQR 1-4] versus 1 [IQR 0-2], p<0.0001). GA use increased from 8% to 56% (p=0.0001) as did use of distal aspiration (59% versus 87%, p=0.0001) mostly in combination with a stent-retriever. Failed access fell from 8% to 3%. When GA was used, successful recanalisation (TICI 2b/3) was achieved more frequently (90.5% versus 76.7%; OR 3.04, 1.2-7.69, p=0.0187). CONCLUSION: Technical results for thrombectomy are improving over time. Technique modification, operator experience, and judicious use of GA may be contributing.

Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients.

AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration. METHODS: Western blot analysis, real-time PCR and immunohistochemistry were performed with muscle tissue from presymptomatic and early-symptomatic male SOD1(G93A) mice and with muscle biopsies of control and sporadic ALS (sALS) patients. Analysed PRRs include nucleotide-binding oligomerization domain-like (NOD-like) receptor protein 1 (NLRP1), NLR protein 3 (NLRP3), NLR family CARD domain-containing 4 (NLRC4) and absent in melanoma 2. Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1ß) and interleukin 18 (IL18) were evaluated. RESULTS: Expression of PRRs and ASC was detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1ß were significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients. Furthermore, levels of caspase 1 and IL1ß were already increased in presymptomatic animals. CONCLUSION: Our findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1ß reflect early changes in the skeletal muscle and may contribute to the denervation process.

AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress.

The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT. The molecular dynamics studies identified important interactions, which may be responsible for the AKT inhibition and efficacy of 3-AWA towards AKT binding pocket. Interestingly, the p21 deceleration was rescued by incubating the cells with 3-AWA in the presence of an ER stress inhibitor, Salubrinal. Furthermore, we demonstrated that p21 expression decreases solitarily in Par-4+/+ MEFs; albeit, ER stress-induced JNK activation was observed in both Par-4+/+ and Par-4-/- MEFs. Par-4 knockdown or overexpression studies established that ectopic Par-4 along with ER stress are not sufficient to downregulate p21 in PC-3 cells but are adequate for DU-145 cells and that the ER stress inflicted activation of JNK, inhibition of AKT and Par-4 induction are all crucial to p21 downmodulation by 3-AWA. By using isogenic cell lines, such as HCT-116 p53+/+ and HCT-116 p53-/-, we found that deceleration in p21 expression due to ER stress is p53 independent. Moreover, in orthotopic carcinogen-induced rat colorectal carcinoma model, we found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil.

ALS-Associated Endoplasmic Reticulum Proteins in Denervated Skeletal Muscle: Implications for Motor Neuron Disease Pathology.

Alpha-motoneurons and muscle fibres are structurally and functionally interdependent. Both cell types particularly rely on endoplasmic reticulum (ER/SR) functions. Mutations of the ER proteins VAPB, SigR1 and HSP27 lead to hereditary motor neuron diseases (MNDs). Here, we determined the expression profile and localization of these ER proteins/chaperons by immunohistochemistry and immunoblotting in biopsy and autopsy muscle tissue of patients with amyotrophic lateral sclerosis (ALS) and other neurogenic muscular atrophies (NMAs) and compared these patterns to mouse models of neurogenic muscular atrophy. Postsynaptic neuromuscular junction staining for VAPB was intense in normal human and mouse muscle and decreased in denervated Nmd2J mouse muscle fibres. In contrast, VAPB levels together with other chaperones and autophagy markers were increased in extrasynaptic regions of denervated muscle fibres of patients with MNDs and other NMAs, especially at sites of focal myofibrillar disintegration (targets). These findings did not differ between NMAs due to ALS and other causes. G93A-SOD1 mouse muscle fibres showed a similar pattern of protein level increases in denervated muscle fibres. In addition, they showed globular VAPB-immunoreactive structures together with misfolded SOD1 protein accumulations, suggesting a primary myopathic change. Our findings indicate that altered expression and localization of these ER proteins and autophagy markers are part of the dynamic response of muscle fibres to denervation. The ER is particularly prominent and vulnerable in both muscle fibres and alpha-motoneurons. Thus, ER pathology could contribute to the selective build-up of degenerative changes in the neuromuscular axis in MNDs.

Reprogramming of Molecular Switching Events in UPR Driven ER Stress: Scope for Development of Anticancer Therapeutics.

The incitement of unfolded protein response (UPR) during endoplasmic reticulum (ER) stress by diverse intracellular (hypoxia, nutrient deprivation, etc.) or extracellular (environmental or drug induced) stimuli is considered a major threat for perturbing cellular homeostasis leading to the aggregation of unfolded proteins inside the cell. The catastrophic UPR events emerge as a prime cellular adaptation by remodeling cancer cell signaling and restoring ER homeostasis in favor of tumor growth. The transient ER stress protects cancer cells from undergoing apoptosis, whereas the prolonged stress response further activates many cell death pathways. The present review summarizes the UPR mediated triggering of transcriptional and translational reprogramming, which will provide novel therapeutic strategies towards pro-death mechanisms rather than a cellular adaptation in tumorigenesis. Nonetheless, the current topic also points out the reprogramming of emerging molecular switching events by complex UPR-mediated signaling to trigger apoptosis. The novel agents from various natural, semi-synthetic and synthetic sources that target ER stress signaling pathway to modulate selectively the UPR phenomena with preclinical efficacy are outlined. Since major emphasis on ER stress-induced transcriptional and translational reprogramming remains to be explored, we believe that the current subject will instigate more attention from the biomedical researchers in this certain research direction.

Complete Bilateral Calcified Psoas Abscess- Rare Sequelae of Untreated Pott's Spine.

Although rare in the western world; psoas abscess is a frequent finding in Indian sub continent associated with Pott's spine. Untreated Pott's spine may lead to various sequelae like destruction of vertebra, kyphosis, paraplageia etc which in modern world is amenable to anti-tubercular drugs and surgical management. We report a case of untreated Pott's spine with bilateral calcified psoas abscess with kyphosis. To the best of our knowledge no such case of complete bilateral calcified psoas abscesses has been reported earlier. We want to discuss this case with relevant literature review and its influence on treatment plan.

Isotopic ratio correlation for the isotopic composition analysis of plutonium in Am-Pu mixed samples having high americium content.

Interference of high amount of americium in the plutonium isotopic composition analysis has been studied by simulating gamma-ray spectra for Am-Pu samples over a wide composition range (5-97% (241)Am) for both power and research reactor grade plutonium. An alternate way for isotopic composition analysis has been proposed by correlating the isotopic ratios available in our old database with the experimentally obtained (241)Pu/(239)Pu isotopic ratio. The proposed method has been validated using simulated spectra of known isotopic compositions.

Tumour necrosis factor-alpha and nitric oxide response in different categories of tuberculosis patients.

OBJECTIVE: To compare the magnitude of tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) response in different categories of active tuberculosis (TB) patients by ex vivo experiment. DESIGN: New, relapsed (recurrent), miliary and pleural effusion TB cases were recruited with matched healthy controls. TNF-α and NO were measured from the culture supernatant of peripheral blood monocytes derived from cases and controls with and without challenge with live Mycobacterium tuberculosis H37Rv. RESULTS: TNF-α and NO production varied significantly among the different categories of TB patients. The magnitude was highest among patients with pleural effusion and lowest in miliary TB cases. In between, progressive decreases in response were noted in new and relapse cases. Overall, positive correlations between TNF-α and NO were noted among the diseased and healthy groups. CONCLUSION: Distinct TNF-α and NO levels appear to be associated with different clinical forms of TB and might help to assess prognosis and contribute to a better understanding of underlying immunopathological mechanisms.

Supramolecular reactive sulphur nanoparticles: a novel and efficient antimicrobial agent.

Antimicrobial resistance continues to be an inexorable threat for the biomedical and biochemical researchers. Despite the novel discoveries in drug designing and delivery, high-throughput screening and surveillance data render the prospects for new antimicrobial agents as bleak as ever. The advent of nanotechnology, however, strengthens pharmacology by offering effective therapeutics to treat this aforementioned problem. Several nanoparticles of the known elements have already been reported for their antimicrobial efficacy. Nanosized fabrication of elemental sulphur with suitable surface modifications offers to retrieve the use of sulphur (man's oldest known ecofriendly microbicide) as a potential antimicrobial agent. Sulphur nanoparticles (SNPs) are effective against both conventionally sulphur-resistant and sulphur-susceptible microbes (fungi and bacteria). Moreover, biocompatible polymers present on the surface of SNPs minimize toxicity during application. Here, we focus on various aspects of physicochemical features of SNPs and their biochemical interactions with microbes. The present review also illustrates the effects of SNPs on plants and animals in terms of cytotoxicity and biocompatibility.

Temperature dependence of ion and water diffusion in crown ether loaded Nafion matrix.

Temperature dependence study of the self-diffusion coefficient of Cs(+) ion in dibenzo-18-crown-6 (DB18C6) modified Nafion-117 (Cs-Naf-CR) was carried out in the temperature range of 50-65 °C. Temperature dependence of water diffusion in Cs-Naf-CR was also studied to understand the mechanism of cation and water transport in the membrane. Because of the very slow kinetics of isotopic exchange, self-diffusion measurement of Na(+) in Na-Naf-CR was carried out only at 60 °C. The result indicates that self-diffusion behavior is governed by the nature of the cation in which the crown ether was loaded in the membrane matrix. The activation energy of diffusion for Cs(+) ion and water in Cs-Naf-CR was found to be much higher than that in the pure Cs(+) form of Nafion (Cs-Naf). Water uptake of the membrane was also found to have reduced compared to Cs/Na-Naf. The results point to the binding of the ions by DB18C6 and the destruction of the water channels in the crown ether loaded membrane. The differential scanning calorimetry (DSC) data supports these observations.

Does extracorporeal shock wave lithotripsy cause hearing impairment? Evaluation by transient evoked otoacoustic emissions.

OBJECTIVE: To evaluate if multiple sessions of extracorporeal shock wave lithotripsy (ESWL) have any effect on the transient evoked otoacoustic emissions (TEOAEs). STUDY DESIGN: Prospective study. SETTING: Academic tertiary medical centre. METHODS: Thirty patients undergoing multiple sessions of ESWL for urinary stone disease were assessed using TEOAEs before and after ESWL. RESULTS: It was found that ESWL does not cause any significant changes in TEOAEs. CONCLUSIONS: ESWL is a safe procedure and does not cause any changes in TEOAEs.

The correlated evolution of Runx2 tandem repeats, transcriptional activity, and facial length in carnivora.

To assess the ability of protein-coding mutations to contribute to subtle, inter-specific morphologic evolution, here, we test the hypothesis that mutations within the protein-coding region of runt-related transcription factor 2 (Runx2) have played a role in facial evolution in 30 species from a naturally evolving group, the mammalian order Carnivora. Consistent with this hypothesis, we find significant correlations between changes in Runx2 glutamine-alanine tandem-repeat ratio, and both Runx2 transcriptional activity and carnivoran facial length. Furthermore, we identify a potential evolutionary mechanism for the correlation between Runx2 tandem repeat ratio and facial length. Specifically, our results are consistent with the Runx2 tandem repeat system providing a flexible genetic mechanism to rapidly change the timing of ossification. These heterochronic changes, in turn, potentially act on existing allometric variation in carnivoran facial length to generate the disparity in adult facial lengths observed among carnivoran species. Our results suggest that despite potentially great pleiotropic effects, changes to the protein-coding regions of genes such as Runx2 do occur and have the potential to affect subtle morphologic evolution across a diverse array of species in naturally evolving lineages.

Serum ferritin in renal cell carcinoma: effect of tumor size, volume grade, and stage.

AIM: To study the levels of serum ferritin in patients of renal cell carcinoma (RCC). PATIENTS AND METHODS: Serum ferritin levels were measured preoperatively in 32 patients with radiological evidence of RCC using an enzyme immunoassay. The largest diameter of the primary tumor was measured in the pathological specimens in patients undergoing radical nephrectomy while in patients with non-operable tumor maximum tumor dimension was taken from CT scan. Pathological staging was done according TNM-1997. RESULTS: Mean serum ferritin value in patients of RCC was 283.23+/-77.38 ng/ml while in controls the mean value was 79.98+/-32.96 ng/ml (P CONCLUSIONS: Serum ferritin levels are elevated in patients with RCC although its actual source is unclear. Further studies are needed to establish the role of ferritin in RCC.

Primary transitional cell carcinoma of the prostate presenting as a rectal ulcer.

Primary transitional cell carcinoma of the prostate is a rare clinicopathological entity. It is an aggressive tumor with a poor prognosis. Presentation is usually late, with obstructive voiding complaints. Radical surgery offers locoregional control of the disease. We report a case with an atypical presentation of bleeding per rectum and associated obstructive voiding symptoms. Examination revealed a rectal ulcer overlying an enlarged prostate and fixed to it. Histopathology showed a picture of transitional cell carcinoma of the prostate infiltrating the rectum. Imaging studies revealed an enlarged prostate with altered echo pattern with locoregional spread, infiltrating the rectum. Bladder involvement and distant metastases were not evident. External beam radiotherapy achieved good local control. At 3 months of follow-up, the patient was free of urinary symptoms and his rectal ulcer had healed. The patient declined subsequent treatment.

Reninoma treated with nephron-sparing surgery.

A 14-year-old hypertensive boy was evaluated in our clinic. The physical examination was essentially normal except for his high blood pressure. Laboratory findings showed increased plasma renin activity. Abdominal ultrasonography detected a hypoechoic, 2-cm mass in right kidney. Contrast-enhanced computed tomography of the abdomen revealed a well-circumscribed, solid, hypoenhancing cortical lesion in the middle of the right kidney. Magnetic resonance angiography documented bilateral normal renal arteries. With a preoperative diagnosis of reninoma, the patient underwent nephron-sparing surgery. Intraoperative frozen section analysis revealed a benign lesion. Subsequently, histopathologic examination and electron microscopy confirmed the diagnosis of juxtaglomerular cell tumor. The patient remained normotensive in the postoperative period. Follow-up intravenous urography showed bilateral normally functioning kidneys.

Cervical percutaneous laser disc decompression: preliminary results of an ongoing prospective outcome study.

OBJECTIVE: This study identifies the efficacy of laser disc ablation and compares the relative efficacy of Holmium2100; YAG and KTP532 laser wavelengths in the treatment of broad-based cervical disc protrusions presenting with cervical axial pain with compressive or noncompressive radicular symptoms. BACKGROUND: A preliminary report on a prospective outcome study of cervical laser disc ablation and decompression in the management of cervical disc prolapse and discographically confirmed discogenic pain in association with radicular pain. METHODS: Patients with chronic cervical pain and radicular symptoms unresponsive to conservative treatment were assessed with magnetic resonance (MR) scans. Those with broad-based disc bulge or discal degeneration were assessed with provocative discography to isolate the source of pain. Percutaneous laser disc decompression was performed as a day case procedure on 105 patients at 108 levels under X-ray control via the anterior approach with side-firing probes in patients. RESULTS: At a minimum follow up of 24 months, 51% of patients demonstrated a sustained significant clinical benefit with an additional 25% in whom functional improvement was noted. No difference in outcome was identified either with the wavelengths used or with laser annealing or painful discal tears. The cohort integrity of the study was 80%. CONCLUSION: The sustained nature of the benefit (mean 3.5 years at final follow up) after long-term preoperative symptoms (mean 3.9 years) in 76% patients rules out placebo effect. Benefits occurred independently of the wavelength of laser used.

Blood lactate concentration at selected of olympic modes weightlifting.

This study highlights the blood lactate response of weightlifters (N = 5) in two modes of olympic lifts: Snatch (SN) and Clean & Jerk (CJ), during three types of training namely (1) one repetition lift (ORL), (2) Multiple set session (MSS) and (3) one set session (OSS). In ORL, 30, 40, 50, and 60 kg, each of one repetition only, were lifted with an interval of 5 min between two consecutive loads. Both MSS and OSS consisted of 6 sets of lift: 50% x 6 (i.e. 50% of 1 Repetition Maximum x 6 repetitions), 60% x 5, 70% x 4, 80% x 3, 90% x 2, and 100% x 1. In MSS, 3 to 3.5 min interval was given between two successive sets whereas in OSS the interval was approximately 24 hours. Lactate levels were very low (< 3.5 mM) in ORL. In MSS, lactate reached peak at an intermediate set, but, it was maximum at the first set and then declined gradually in OSS. In most of the cases, however, lactate were significantly higher in CJ than SN. The study concludes that: (a) anaerobic glycolysis is not stimulated considerably when the lifting time is only 4-5 sec, (b) repetition of lift plays more important role, than intensity, in lactate production, (c) CJ is more strenuous than SN for a given %RM.

Endoscopic foraminoplasty: a prospective study on 250 consecutive patients with independent evaluation.

OBJECTIVE: This study focused on the efficacy of endoscopic decompression of the foramen guided by endoscopic aware-state pain source definition. BACKGROUND DATA: Endoscopic foraminoplasty consists of undercutting of the facet joint and endoscopic discectomy, mobilization and neurolysis of the exiting and transiting nerves, and ablation of osteophytes. This study sought the outcome of endoscopic foraminoplasty in 250 consecutive patients followed for a minimum of 2 years, reviewed and assessed by an external independent assessor. It was applied to patients with back pain and sciatica in multilevel degenerative disc disease and also to those with prior surgery. METHODS: A prospective study of endoscopic laser foraminoplasty was performed on 121 males and 129 females with an average age of 48 years (21-86 years), followed for an average period of 30 months (26-43 months). The average preoperative duration of back, buttock, or leg pain was 6.1 years (5-11 years). A total of 30% had undergone prior open spinal surgery. RESULTS: The cohort integrity at follow up was 97%. Outcome was analyzed using the percentage change in Oswestry Disability Scores and visual analogue pain scores. Clinically relevant change in pain and disability was observed in 73%. Using a percentage change in Oswestry Disability Score of 50 or more to determine good and excellent outcomes, 60% of patients exceeded this score. A total of 95% patients required no further surgical intervention. CONCLUSIONS: Endoscopic laser foraminoplasty provides a minimalist means of exploring the extraforaminal zone, the foramen, the disc, and the epidural space and performing discectomy, lateral recess decompression, osteophytectomy, and neural mobilization. Performed in the aware state, it serves to identify and localize precisely the causal source of pain in multilevel disc disease, in revision surgery, and in the infirm and elderly without open fusion or decompression.

Review of safety in endoscopic laser foraminoplasty for the management of back pain.

OBJECTIVE: The purpose of this study was to analyze the incidence and gravity of reported complications that arise in spinal surgery and assess the comparative safety, or otherwise, of endoscopic laser foraminoplasty (ELF). BACKGROUND DATA: Chemonucleolysis, decompression, discectomy, and fusion have long been cited as treatments for chronic low back pain. Over recent years newer, less invasive surgical techniques have become available, one such being ELF. Although minimally invasive, the beneficial outcome must be interpreted in relation to concerns regarding the safety of the procedure and its risks relative to those of other forms of spinal surgery. The Spinal Foundation, Rochdale has performed 958 ELFs and has collated a comprehensive database of the results of all these operations. These prospective records provided the basis for a comparison of the safety of ELF to that reported with other spinal surgical techniques. METHODS: A total of 958 procedures have been performed on 716 patients. Complications that arose during the operation and the postoperative phase of 6 weeks following the procedure were elicited from patient records. These data were correlated and compared to a meta-analysis of randomized controlled clinical trial data of complications arising during and after conventional spinal surgery. The SPSS (statistical package for social sciences) and CIA (confidence interval analysis) statistical packages were used to draw conclusions regarding the safety of ELF. RESULTS: The cohort integrity of operation and outpatient review records at 6 weeks after surgery was 100%. In 958 ELFs performed, 24 complications occurred in 23 patients. There were 9 cases of discitis (1 infective, 8 aseptic) (0.9%), 1 dural tear (0.1%), 1 deep wound infection (0.1%), 2 patients suffered a foot drop (1 transient) (0.2%), 1 myocardial infarction (0.1%), 1 erectile dysfunction (0.1%), and 1 patient who developed panic attacks post-operatively (0.1%). This amounts to an overall surgical complication rate of 1.6%. Magnetic resonance imaging (MRI) follow up of clinically symptomatic patients highlighted 8 residual disc herniations (0.8%). Meta-analysis of randomized controlled trials of conventional spinal surgery for adult onset degenerative disc disease and/or sciatic pain reported overall complication rates for fusion (11.8%), decompression (7.6%), discectomy (6.0%), and chemonucleolysis (9.6%). CONCLUSIONS: The complication rate of ELF is shown to be significantly lower than that reported following conventional spinal surgery (p < 0.01). From these results, we conclude that ELF as a treatment for chronic low back pain and sciatica presents less risk to a patient than conventional methods of spinal surgery.