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1.  Screening for proteinuria in ‘at-risk’ patients with spinal cord injuries: lessons learnt from failure 
Spinal cord injury patients may develop proteinuria as a result of glomerulosclerosis due to urosepsis, hydronephrosis, vesicoureteric reflux, and renal calculi. Proteinuria in turn contributes to progression of kidney disease. We report one paraplegic and two tetraplegic patients, who developed recurrent urine infections, urinary calculi, and hydronephrosis. These patients required several urological procedures (nephrostomy, cystoscopy and ureteric stenting, ureteroscopy and lithotripsy, extracorporeal shock wave lithotripsy). These patients had not received antimuscarinic drugs nor had they undergone video-urodynamics. Proteinuria was detected only at a late stage, as testing for proteinuria was not performed during follow-up visits. Urine electrophoresis showed no monoclonal bands in any; Serum glomerular basement membrane antibody screen was negative. Serum neutrophil cytoplasmic antibodies screen by fluorescence was negative. All patients were prescribed Ramipril 2.5 mg daily and there was no further deterioration of renal function.
Spinal cord injury patients, who did not receive antimuscarinic drugs to reduce intravesical pressure, are at high risk for developing reflux nephropathy. When such patients develop glomerulosclerosis due to recurrent urosepsis, renal calculi, or hydronephrosis, risk of proteinuria is increased further. Take home message: (1) Screening for proteinuria should be performed regularly in the ‘at-risk’ patients. (2) In the absence of other renal diseases causing proteinuria, spinal cord injury patients with significant proteinuria may be prescribed angiotensin-converting enzyme inhibitor or angiotensin-II receptor antagonist to slow progression of chronic renal disease and reduce the risk of cardiovascular mortality.
doi:10.1186/1754-9493-8-25
PMCID: PMC4064104  PMID: 24955116
Spinal cord injury; Proteinuria; Kidney; Renal calculi
3.  Carcinoma transverse colon masquerading as carcinoma gall bladder 
Colorectal cancer is one of the most common cancer worldwide .Its incidence is reported to be increasing in developing countries. It commonly presents with weight loss, anaemia, lump abdomen, change of bowel habit, obstruction or fresh rectal bleeding. Beside these common modes of presentations, there are some rare manifestations which masqueraded as different disease like obstructive jaundice, empyema gall bladder or cholecystitis. A 60-year-old male presented to hospital with right sided pain abdomen. On abdominal examination mild tenderness was present in right hypochondrium. Intra operatively gall bladder was separated from the adjoining gut, peritoneum and liver bed and was removed. On further exploration, there was a large mass in the vicinity of the gall bladder related to transverse colon. Extended right hemicolectomy was done. Histopathological examination of gut mass revealed adenocarcinoma of transverse colon with free margins and gall bladder showed cholecystitis with no evidence of malignancy. We present an interesting case of colon cancer colon that caused diagnostic confusion by mimicking as cholecystitis. Colorectal cancer constitutes a major public health issue globally. Therefore, public awareness, screening of high-risk populations, early diagnosis and effective treatment and follow-up will help to reduce its occurance and further complications.
doi:10.3978/j.issn.2078-6891.2014.009
PMCID: PMC3999631  PMID: 24772345
Cholecystitis; colon cancer; transverse colon; cholecystectomy; chemotherapy
4.  Cytotoxic and antimicrobial activities of endophytic fungi isolated from Bacopa monnieri (L.) Pennell (Scrophulariaceae) 
Background
Endophytes, which reside in plant tissues, have the potential to produce novel metabolites with immense benefits for health industry. Cytotoxic and antimicrobial activities of endophytic fungi isolated from Bacopa monnieri (L.) Pennell were investigated.
Methods
Endophytic fungi were isolated from the Bacopa monnieri. Extracts from liquid cultures were tested for cytotoxicity against a number of cancer cell lines using the MTT assay. Antimicrobial activity was determined using the micro dilution method.
Results
22% of the examined extracts showed potent (IC50 of <20 μg/ml) cytotoxic activity against HCT-116 cell line. 5.5%, 11%, 11% of the extracts were found to be cytotoxic for MCF-7, PC-3, and A-549 cell lines respectively. 33% extracts displayed antimicrobial activity against at least one test organism with MIC value 10–100 μg/ml. The isolate B9_Pink showed the most potent cytotoxic activity for all the cell lines examined and maximum antimicrobial activity against the four pathogens examined which was followed by B19.
Conclusions
Results indicated the potential for production of bioactive agents from endophytes of Bacopa monnieri.
doi:10.1186/1472-6882-14-52
PMCID: PMC3930298  PMID: 24512530
Bacopa monnieri; Endophytic fungi; MTT assay; Antimicrobial activity; Cytotoxicity; HCT-116
5.  Substandard urological care of elderly patients with spinal cord injury: an unrecognized epidemic? 
Background
We report the anecdotal observation of substandard urological care of elderly paraplegic patients in the community suffering from long-term sequelae of spinal cord injuries. This article is designed to increase awareness of a problem that is likely underreported and may represent the ‘tip of the iceberg’ related to substandard care provided to the vulnerable population of elderly patients with chronic neurological impairment.
Findings
A registered Nurse changed the urethral catheter of an 80-year-old-male with paraplegia; patient developed profuse urethral bleeding and septicaemia. Ultrasound revealed balloon of Foley catheter located in membranous urethra. Flexible cystoscopy was performed and a catheter was inserted over a guide wire. Urethral bleeding recurred 12 days later. This patient was discharged after protracted stay in spinal unit. A nurse changed urethral catheter in an 82-year-old male with paraplegia. The catheter did not drain urine; patient developed pain in lower abdomen. The balloon of Foley catheter was visible behind the urethral meatus, which indicated that the balloon had been inflated in penile urethra. The catheter was removed and a 16 French Foley catheter was inserted per urethra. About 1300 ml of urine was drained. A 91-year-old lady with paraplegia underwent routine ultrasound examination of urinary tract by a Consultant Radiologist, who reported a 4 cm × 3 cm soft tissue mass in the urinary bladder. Cystoscopy was performed without anaesthesia in lithotomy position. Cystoscopy revealed normal bladder mucosa; no stones; no tumour. Following cystoscopy, the right knee became swollen and there was deformity of lower third of right thigh. X-ray revealed fracture of lower third of right femur. Femoral fracture was treated by immobilisation in full plaster cast. Follow-up ultrasound examination of urinary tract, performed by a senior Radiologist, revealed normal outline of urinary bladder with no tumour or calculus.
Conclusion
The adverse outcomes can be averted if elderly spinal cord injury patients are treated by senior, experienced health professionals, who are familiar with changes in body systems due to old age, compounded further by spinal cord injury.
doi:10.1186/1754-9493-8-4
PMCID: PMC3899400  PMID: 24447309
Spinal cord injury; Elderly patients; Substandard care
6.  Candida albicans Fungaemia following Traumatic Urethral Catheterisation in a Paraplegic Patient with Diabetes Mellitus and Candiduria Treated by Caspofungin 
A 58-year-old paraplegic male, with long-term indwelling urethral catheter, developed catheter block. The catheter was changed, but blood-stained urine was drained intermittently. A long segment of the catheter was seen lying outside his penis, which indicated that the balloon of Foley catheter had been inflated in urethra. The misplaced catheter was removed and a new catheter was inserted correctly. Gentamicin 160 mg was given intravenously; meropenem 1 gram every eight hours was prescribed; antifungals were not given. Twenty hours later, this patient developed distension of abdomen, tachycardia, and hypotension; he was not arousable. Computed tomography of abdomen revealed inflamed uroepithelium of right renal pelvis and ureter, 4 mm lower ureteric calculus with gas in right ureter proximally, and vesical calculus containing gas in its matrix. Urine and blood culture yielded Candida albicans. Identical sensitivity pattern of both isolates suggested that the source of the bloodstream infection was most likely urine. Both isolates formed consistently high levels of biofilm formation in vitro as assessed using a biofilm biomass stain, and high levels of resistance to voriconazole were observed. Both amphotericin B and caspofungin showed good activity against the biofilms. HbA1c was 111 mmol/mol. This patient was prescribed human soluble insulin and caspofungin 70 mg followed by 50 mg daily intravenously. He recovered fully from candidemia.
doi:10.1155/2013/693480
PMCID: PMC3816213  PMID: 24223316
7.  Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction 
The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction.
doi:10.4103/0970-1591.120116
PMCID: PMC3822350  PMID: 24235796
Botulinum toxin; clam augmentation; clam cystoplasty; conduit urinary diversion; continent diversion; detrusor myomectomy; enterocystoplasy; ileocystoplasty; long-term outcome; neobladder; neurogenic; reconstruction; review; sphincterotomy; spinal cord injury; urethral stent; urinary tract dysfunction
8.  Failure of Urological Implants in Spinal Cord Injury Patients due to Infection, Malfunction, and Implants Becoming Obsolete due to Medical Progress and Age-Related Changes in Human Body Making Implant Futile: Report of Three Cases 
Case Reports in Urology  2013;2013:826748.
Any new clinical data, whether positive or negative, generated about a medical device should be published because health professionals should know which devices do not work, as well as those which do. We report three spinal cord injury patients in whom urological implants failed to work. In the first, paraplegic, patient, a sacral anterior root stimulator failed to produce erection, and a drug delivery system for intracavernosal administration of vasoactive drugs was therefore implanted; however, this implant never functioned (and, furthermore, such penile drug delivery systems to produce erection had effectively become obsolete following the advent of phosphodiesterase type 5 inhibitors). Subsequently, the sacral anterior root stimulator developed a malfunction and the patient therefore learned to perform self-catheterisation. In the second patient, also paraplegic, an artificial urinary sphincter was implanted but the patient developed a postoperative sacral pressure sore. Eight months later, a suprapubic cystostomy was performed as urethral catheterisation was very difficult. The pressure sore had not healed completely even after five years. In the third case, a sacral anterior root stimulator was implanted in a tetraplegic patient in whom, after five years, a penile sheath could not be fitted because of penile retraction. This patient was therefore established on urethral catheter drainage. Later, infection with Staphylococcus aureus around the receiver block necessitated its removal. In conclusion, spinal cord injury patients are at risk of developing pressure sores, wound infections, malfunction of implants, and the inability to use implants because of age-related changes, as well as running the risk of their implants becoming obsolete due to advances in medicine. Some surgical procedures such as dorsal rhizotomy are irreversible. Alternative treatments such as intermittent catheterisations may be less damaging than bladder stimulator in the long term.
doi:10.1155/2013/826748
PMCID: PMC3705782  PMID: 23864980
9.  Oophorectomy in Breast Cancer—Controversies and Current Status 
The Indian Journal of Surgery  2012;74(3):210-212.
The role of oophorectomy in the treatment of breast cancer is known for over 100 years. Ovarian ablation has a relatively large positive effect on both disease-free survival (DFS) and overall survival (OS) in premenopausal women when compared to no adjuvant treatment. Today the standard of care in adjuvant therapy of endocrine responsive tumors in premenopausal women is tamoxifen with or without chemotherapy. The role of oophorectomy /ovarian ablation in current surgical practice is discussed and important issues highlighted in the article.
doi:10.1007/s12262-012-0584-7
PMCID: PMC3397181  PMID: 23730045
Oophorectomy; Ovarian ablation; Breast cancer
10.  Expression of γH2AX may help in defining a genetically more stable subtype of infiltrating ductal carcinoma of breast 
Background & objectives:
Gamma H2AX, a marker of DNA double stranded breaks (DSB) has been found to be over expressed in various tumours. The objective of the present work was to study the expression of γH2AX in infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) cases and to associate the expression in IDC with cytomorphological features and DNA ploidy.
Methods:
The expression of γH2AX was studied in fine needle aspirates of 16 cases of IDC and 15 FA cases. The expression in IDC was correlated with the cytological grade, apoptotic (AI) and mitotic indices (MI) and ploidy status.
Results:
A high γH2AX expression was noted in IDC as compared to FA. Amongst the IDC cases the γH2AX was found to be significantly over expressed in DNA diploid IDC cases as compared to the aneuploid ones.
Interpretation & conclusions:
The study suggests a role of γH2AX in breast carcinogenesis which needs to be explored further. Moreover, the γH2AX expression together with ploidy status may serve as a means of assigning the patients of IDC to a better prognostic category irrespective of the cytomorphogical parameters.
PMCID: PMC3724258  PMID: 23703345
Apoptosis; cytology; fibroadenoma; γH2AX; grading; IDC; ploidy
11.  Postoperative Complications Leading to Death after Coagulum Pyelolithotomy in a Tetraplegic Patient: Can We Prevent Prolonged Ileus, Recurrent Intestinal Obstruction due to Adhesions Requiring Laparotomies, Chest Infection Warranting Tracheostomy, and Mechanical Ventilation? 
Case Reports in Urology  2013;2013:682316.
A 22-year-old male sustained C-6 tetraplegia in 1992. In 1993, intravenous pyelography revealed normal kidneys. Suprapubic cystostomy was performed. He underwent open cystolithotomy in 2004 and 2008. In 2009, computed tomography revealed bilateral renal calculi. Coagulum pyelolithotomy of left kidney was performed. Pleura and peritoneum were opened. Peritoneum could not be closed. Following surgery, he developed pulmonary atelectasis; he required tracheostomy and mechanical ventilation. He did not tolerate nasogastric feeding. CT of abdomen revealed bilateral renal calculi and features of proximal small bowel obstruction. Laparotomy revealed small bowel obstruction due to dense inflammatory adhesions involving multiple small bowel loops which protruded through the defect in sigmoid mesocolon and fixed posteriorly over the area of previous intervention. All adhesions were divided. The wide defect in mesocolon was not closed. In 2010, this patient again developed vomiting and distension of abdomen. Laparotomy revealed multiple adhesions. He developed chest infection and required ventilatory support again. He developed pressure sores and depression. Later abdominal symptoms recurred. This patient's general condition deteriorated and he expired in 2011. Conclusion. Risk of postoperative complications could have been reduced if minimally invasive surgery had been performed instead of open surgery to remove stones from left kidney. Suprapubic cystostomy predisposed to repeated occurrence of stones in urinary bladder and kidneys. Spinal cord physicians should try to establish intermittent catheterisation regime in tetraplegic patients.
doi:10.1155/2013/682316
PMCID: PMC3600272  PMID: 23533931
12.  Author's reply 
Indian Journal of Anaesthesia  2013;57(1):93-94.
doi:10.4103/0019-5049.108591
PMCID: PMC3658356  PMID: 23716785
13.  Fatal Renal Failure in a Spinal Cord Injury Patient with Vesicoureteric Reflux Who Underwent Repeated Ureteric Reimplantations Unsuccessfully: Treatment Should Focus on Abolition of High Intravesical Pressures rather than Surgical Correction of Reflux 
Case Reports in Urology  2012;2012:603715.
A 29-year-old man developed paraplegia at T-10 level due to road traffic accident in 1972. Both kidneys were normal and showed good function on intravenous urography. Division of external urethral sphincter was performed in 1973. In 1974, cystogram showed retrograde filling of left renal tract, which was hydronephrotic. Left ureteric reimplantation was performed. Following surgery, cystogram revealed marked retrograde filling of left renal tract as before. Penile sheath drainage was continued. In 1981, intravenous urography revealed bilateral severe hydronephrosis. Left ureteric reimplantation was performed again in 1983. Blood pressure was 220/140 mm Hg; this patient was prescribed atenolol. Cystogram showed gross left vesicoureteral reflux. Intermittent catheterisation was commenced in 2001. In 2007, proteinuria was 860 mg/day. This patient developed progressive renal failure and expired in 2012. In a spinal cord injury patient with vesicoureteral reflux, the treatment should focus on abolition of high intravesical pressures rather than surgical correction of vesicoureteric reflux. Detrusor hyperactivity and high intravesical pressures are the basic causes for vesicoureteral reflux in spinal cord injury patients. Therefore, it is important to manage spinal cord injury patients with neuropathic bladder by intermittent catheterisations along with antimuscarinic drug therapy in order to abolish high detrusor pressures and prevent vesicoureteral reflux. Angiotensin-converting enzyme inhibitors or angiotensin-receptor-blocking agents should be prescribed even in the absence of hypertension when a spinal cord injury patient develops vesicoureteral reflux and proteinuria.
doi:10.1155/2012/603715
PMCID: PMC3595704  PMID: 23509659
14.  Tissue Doppler imaging for diagnosis of coronary artery disease: a systematic review and meta-analysis 
Global and regional left ventricular (LV) systolic dysfunction is a marker of coronary artery disease (CAD), which is conventionally assessed using two-dimensional echocardiography. Tissue Doppler imaging (TDI) has emerged as an adjunct tool in the diagnosis of regional wall motion abnormalities from CAD. We performed a systematic review and meta-analysis to assess the efficacy of TDI indices in the diagnosis of CAD. We searched MEDLINE and the Cochrane Library for controlled studies comparing TDI measurements in those with and without CAD as confirmed by coronary angiography. Meta-analyses of mean differences in TDI velocities between these populations were performed. Screening of titles and abstracts followed by full-text screening identified 8 studies. At rest, TDI was associated with a significant decrease in the pooled maximum systolic velocity among CAD patients compared to those without CAD [mean difference (MD): -0.66; 95% confidence interval (CI): -0.98 to −0.34]. There were no significant differences in maximum early and late diastolic velocities. Post-stress, TDI was associated with a significant decrease in maximum early diastolic velocity (MD: -1.91; 95% CI: -2.74 to −1.09) and maximum late diastolic velocity (MD: -1.57; 95% CI: -2.95 to −0.18) among CAD patients compared to those without CAD. There was no significant difference in maximum systolic velocity post-stress. Our results suggest that TDI may have a role in the evaluation of CAD. Future studies should evaluate the incremental value of TDI velocities over LV ejection fraction and two dimensional wall motion analysis in the detection of CAD and assessment of its severity. (Word Count: 249)
doi:10.1186/1476-7120-10-47
PMCID: PMC3542063  PMID: 23199010
Systematic review; Meta-analysis; Tissue Doppler; Echocardiography; Coronary artery disease
15.  Challenges in Diagnosis and Treatment of a Cervical Spinal Cord Injury Patient with Melanoma, Adenocarcinoma, and Hepatic and Osteolytic Metastases: Need to Implement Strategies for Prevention and Early Detection of Cancer in Spinal Cord Injury Patients 
A male tetraplegic patient with, who had been taking warfarin, developed haematuria. Ultrasound scan revealed no masses, stones, or hydronephrosis. Urinary bladder had normal configuration with no evidence of masses or organised haematoma. Urine cytology revealed no malignant cells. Four months later, CT urography revealed an irregular mass at the base of urinary bladder. Cystoscopic biopsy revealed moderately differentiated adenocarcinoma, which contained goblet cells and pools of mucin showing strongly positive immunostaining for prostatic acid hosphatase and patchy staining for prostate specific antigen. Computed Tomography revealed multiple hypodense hepatic lesions and several osteolytic areas in femoral heads and iliac bone. With a presumptive diagnosis of prostatic carcinoma, leuprorelin acetate 3.75 mg was prescribed. This patient expired a month later. Conclusion. (i) Spinal cord injury patient, who passed blood in urine while taking warfarin, requires repeated investigations to look for urinary tract neoplasm. (ii) Anti-androgen therapy should be prescribed for 2 weeks prior to administration of gonadorelin analogue to prevent tumour flare causing bone pain, bladder outlet obstruction, uraemia, and cardiovascular risk due to hypercoagulability associated with a rapid increase in tumour burden. (iii) Spinal cord physicians should adopt a caring and compassionate approach while managing tetraplegic patients with several co-morbidities, as aggressive diagnostic tests and therapeutic procedures may lead to deterioration in the quality of life.
doi:10.1155/2012/531214
PMCID: PMC3512243  PMID: 23227385
16.  Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins 
The Biochemical journal  2011;439(2):299-311.
Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and tricarboxylic acid (TCA) cycle intermediates into biosynthetic pathways. Because the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell’s ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to nutrient stress that kills cancer cells by becoming quiescent and catabolic. We show that FTY720, a water soluble sphingolipid drug that is effective in many animal cancer models, selectively starves cancer cells to death by down-regulating nutrient transporter proteins. Consistent with a bioenergetic mechanism of action, FTY720 induced homeostatic autophagy. Cells were protected from FTY720 by cell permeable nutrients or by reducing nutrient demand, but blocking apoptosis was ineffective. Importantly, AAL-149, an FTY720 analog that lacks FTY720’s dose limiting toxicity, also triggered transporter loss and killed patient-derived leukemias while sparing cells isolated from normal donors. Because they target the metabolic profile of cancer cells rather than specific oncogenic mutations, FTY720 analogs like AAL-149 should be effective against many different tumor types, particularly in combination with drugs that inhibit autophagy.
doi:10.1042/BJ20110853
PMCID: PMC3454501  PMID: 21767261
bioenergetics; nutrient limitation; autophagy; FTY720; AAL-149
17.  Role of Tc99m-Sestamibi scintimammography in assessing response to neoadjuvant chemotherapy in patients with locally advanced breast cancer 
Introduction:
Neoadjuvant chemotherapy (NACT) is an essential part of multi-disciplinary management of locally advanced breast cancer (LABC). In this study, we aimed at evaluating the role of Tc99m-Sestamibi scinti-mammography in assessing response to NACT in patients with LABC.
Materials and Methods:
A total of 42 patients of histologically proven LABC were enrolled in this prospective study. Imaging was performed according to pre-defined protocol at 10 min and 4 h after injection of tracer before the start of chemotherapy, 48 h after start of chemotherapy and at the end of chemotherapy. Quantitative parameters were obtained by calculating the ratio of activity in a region of interest (ROI) drawn over the tumor and the same sized ROI drawn in corresponding location in contra lateral breast.
Results:
At the end of chemotherapy, 6 patients achieved complete response, 25 achieved partial response, 11 had stable disease. Various retention indices calculated at baseline, 48 h after first cycle of NACT, and at the end of chemotherapy showed statistically significant difference in responders and non-responders. By using 84.05 as cut-off point for retention index (RI) of tumor calculated 48 h after first cycle of NACT (RI 2) the positive predictive value and negative predictive value, were found to be 41.9% and 72.7% respectively in differentiating responders from non-responders.
Conclusion:
Early response assessment in patients with LABC to NACT with Tc99m-Sestamibi scintimammography is feasible and if confirmed by further studies can find routine clinical application in differentiating responders from non-responders.
doi:10.4103/0972-3919.115391
PMCID: PMC3759081  PMID: 24019650
Locally advanced breast cancer; response evaluation; scintimammography; Tc99m-Sestamibi
18.  Hydronephrosis and renal failure following inadequate management of neuropathic bladder in a patient with spinal cord injury: Case report of a preventable complication 
Background
Condom catheters are indicated in spinal cord injury patients in whom intravesical pressures during storage and voiding are safe. Unmonitored use of penile sheath drainage can lead to serious complications.
Case report
A 32-year old, male person, sustained complete paraplegia at T-11 level in 1985. He had been using condom catheter. Eleven years after sustaining spinal injury, intravenous urography showed no radio-opaque calculus, normal appearances of kidneys, ureters and bladder. Blood urea and Creatinine were within reference range. A year later, urodynamics revealed detrusor pressure of 100 cm water when detrusor contraction was initiated by suprapubic tapping. This patient was advised intermittent catheterisation and take anti-cholinergic drug orally; but, he wished to continue penile sheath drainage. Nine years later, this patient developed bilateral hydronephrosis and renal failure. Indwelling urethral catheter drainage was established. Five months later, ultrasound examination of urinary tract revealed normal kidneys with no evidence of hydronephrosis.
Conclusion
Spinal cord injury patients with high intravesical pressure should not have penile sheath drainage as these patients are at risk for developing hydronephrosis and renal failure. Intermittent catheterisation along with antimuscarinic drug should be the preferred option for managing neuropathic bladder.
doi:10.1186/1754-9493-6-22
PMCID: PMC3495664  PMID: 23014062
19.  The Human Transporter Associated with Antigen Processing 
The Journal of Biological Chemistry  2012;287(33):28099-28111.
Background: The transporter associated with antigen processing (TAP) is an ABC transporter whose experimental structure is not known.
Results: We have modeled TAP based on the crystal structures of three related ABC transporters.
Conclusion: We identified a possible peptide binding conformation in the transport cycle of TAP.
Significance: These models help interpret experimental data and give information about the transport cycle of ABC transporters in general.
The human transporter associated with antigen processing (TAP) is a member of the ATP binding cassette (ABC) transporter superfamily. TAP plays an essential role in the antigen presentation pathway by translocating cytosolic peptides derived from proteasomal degradation into the endoplasmic reticulum lumen. Here, the peptides are loaded into major histocompatibility class I molecules to be in turn exposed at the cell surface for recognition by T-cells. TAP is a heterodimer formed by the association of two half-transporters, TAP1 and TAP2, with a typical ABC transporter core that consists of two nucleotide binding domains and two transmembrane domains. Despite the availability of biological data, a full understanding of the mechanism of action of TAP is limited by the absence of experimental structures of the full-length transporter. Here, we present homology models of TAP built on the crystal structures of P-glycoprotein, ABCB10, and Sav1866. The models represent the transporter in inward- and outward-facing conformations that could represent initial and final states of the transport cycle, respectively. We described conserved regions in the endoplasmic reticulum-facing loops with a role in the opening and closing of the cavity. We also identified conserved π-stacking interactions in the cytosolic part of the transmembrane domains that could explain the experimental data available for TAP1-Phe-265. Electrostatic potential calculations gave structural insights into the role of residues involved in peptide binding, such as TAP1-Val-288, TAP2-Cys-213, TAP2-Met-218. Moreover, these calculations identified additional residues potentially involved in peptide binding, in turn verified with replica exchange simulations performed on a peptide bound to the inward-facing models.
doi:10.1074/jbc.M112.381251
PMCID: PMC3431710  PMID: 22700967
ABC Transporter; Molecular Docking; Molecular Dynamics; Molecular Modeling; Multidrug Transporters; Peptide Binding; Transporter Associated with Antigen Processing
20.  Pyonephrosis and urosepsis in a 41-year old patient with spina bifida: Case report of a preventable death 
Background
Urological complications are the major cause of ill health in patients with spina bifida. Urinary sepsis accounted for the majority of admissions in patients with spina bifida. As the patient grows older, changes occur in the adult bladder, leading to increases in storage pressure and consequent risk of deterioration of renal function, which may occur insidiously.
Case presentation
A 34-year-old male spinal bifida patient had been managing neuropathic bladder by penile sheath. Intravenous urography revealed normal kidneys. This patient was advised intermittent catheterisations. But self-catheterisation was not possible because of long, overhanging prepuce and marked spinal curvature. This patient developed repeated urine infections. Five years later, ultrasound examination of urinary tract revealed hydronephrotic right kidney with echogenic debris within the collecting system. There was no evidence of dilatation of the ureter near the vesicoureteric junction. The left kidney appeared normal. There was no evidence of calculus disease seen in either kidney. Indwelling urethral catheter drainage was established.
Two years later, MAG-3 renogram revealed normal uptake and excretion by left kidney. The right kidney showed little functioning tissue. Following a routine change of urethral catheter this patient became unwell. Ultrasound examination revealed hydronephrotic right kidney containing thick hyper-echoic internal septations and debris in the right renal pelvis suspicious of pyonephrosis. Under both ultrasound and fluoroscopic guidance, an 8 French pig tail catheter was inserted into the right renal collecting system. 150 ml of turbid urine was aspirated immediately. This patient developed large left pleural effusion, collapse/consolidation of the left lower lobe, a large fluid collection in the abdomen extending into the pelvis and expired twenty days later because of sepsis and respiratory failure.
Conclusion
Although penile sheath drainage may be convenient for a spina bifida patient and the carers, hydronephrosis can occur insidiously. With recurrent urine infections, hydronephrotic kidney can become pyonephrosis, which is life-threatening. Therefore, every effort should be made to carry out intermittent catheterisations along with antimuscarinic drug therapy.
doi:10.1186/1754-9493-6-10
PMCID: PMC3407709  PMID: 22613462
21.  Intraoperative red blood cell salvage and autologous transfusion during open radical retropubic prostatectomy: a cost–benefit analysis 
INTRODUCTION
Open radical retropubic prostatectomy (RRP) has an average blood loss of over 1,000ml. This has been reported even from high volume centres of excellence.1–4 We have looked at the clinical and financial benefits of using intraoperative cell salvage (ICS) as a method of reducing the autologous blood transfusion requirements for our RRP patients.
MATERIALS AND METHODS
Group A comprised 25 consecutive patients who underwent RRP immediately prior to the acquisition of a cell saver machine. Group B consisted of the next 25 consecutive patients undergoing surgery using the Dideco Electa (Sorin Group, Italy) cell saver machine. Blood transfusion costs for both groups were calculated and compared.
RESULTS
The mean postoperative haemoglobin was similar in both groups (11.1gm/dl in Group A and 11.4gm/dl in Group B). All Group B patients received autologous blood (average 506ml, range: 103–1,023ml). In addition, 5 patients (20%) in Group B received a group total of 16 units (average 0.6 units) of homologous blood. For Group A the total cost of transfusing the 69 units of homologous blood was estimated as £9,315, based on a per blood unit cost of £135. This cost did not include consumables or nursing costs.
CONCLUSIONS
We found no evidence that autologous transfusions increased the risk of early biochemical relapse or of disease dissemination. ICS reduced our dependence on donated homologous blood.
doi:10.1308/003588411X561044
PMCID: PMC3293313  PMID: 22041147
Blood transfusion; Cell saver; Intraoperative cell salvage; Open radical retropubic prostatectomy; Prostate specific antigen
22.  Attenuation of pressor response and dose sparing of opioids and anaesthetics with pre-operative dexmedetomidine 
Indian Journal of Anaesthesia  2012;56(2):123-128.
Background and Aims:
Alpha-2 agonists are being increasingly used as adjuncts in general anaesthesia, and the present study was carried out to investigate the ability of intravenous dexmedetomidine in decreasing the dose of opioids and anaesthetics for attenuation of haemodynamic responses during laryngoscopy and tracheal intubation.
Methods:
One hundred patients scheduled for elective general surgery were randomized into two groups: D and F (n=50 in each group). Group D were administered 1 μg/kg each of dexmedetomidine and fentanyl while group F received 2 μg/kg of fentanyl pre-operatively. Thiopental was given until eyelash reflex disappeared. Anaesthesia was maintained with 33:66 oxygen: nitrous oxide. Isoflurane concentration was adjusted to maintain systolic blood pressure within 20% of the pre-operative values. Haemodynamic parameters were recorded at regular intervals during induction, intubation, surgery and extubation. Statistical analysis was carried out using analysis of variance, chi-square test, Student's t test and Mann–Whitney U test.
Results:
The demographic profile was comparable. The pressor response to laryngoscopy, intubation, surgery and extubation were effectively decreased by dexmedetomidine, and were highly significant on comparison (P<0.001). The mean dose of fentanyl and isoflurane were also decreased significantly (>50%) by the administration of dexmedetomidine. The mean recovery time was also shorter in group D as compared with group F (P=0.014).
Conclusions:
Dexmedetomidine is an excellent drug as it not only decreased the magnitude of haemodynamic response to intubation, surgery and extubation but also decreased the dose of opioids and isoflurane in achieving adequate analgesia and anaesthesia, respectively.
doi:10.4103/0019-5049.96303
PMCID: PMC3371485  PMID: 22701201
Dexmedetomidine; fentanyl; heart rate; isoflurane; mean arterial pressure; pressor response
23.  Are urological procedures in tetraplegic patients safely performed without anesthesia? a report of three cases 
Background
Some tetraplegic patients may wish to undergo urological procedures without anaesthesia, but these patients can develop autonomic dysreflexia if cystoscopy and vesical lithotripsy are performed without anaesthesia.
Case presentation
We describe three tetraplegic patients, who developed autonomic dysreflexia when cystoscopy and laser lithotripsy were carried out without anesthesia.
In two patients, who declined anaesthesia, blood pressure increased to more than 200/110 mmHg during cystoscopy. One of these patients developed severe bleeding from bladder mucosa and lithotripsy was abandoned. Laser lithotripsy was carried out under subarachnoid block a week later in this patient, and this patient did not develop autonomic dysreflexia.
The third patient with C-3 tetraplegia had undergone correction of kyphoscoliotic deformity of spine with spinal rods and pedicular screws from the level of T-2 to S-2. Pulmonary function test revealed moderate to severe restricted curve. This patient developed vesical calculus and did not wish to have general anaesthesia because of possible need for respiratory support post-operatively. Subarachnoid block was not considered in view of previous spinal fixation. When cystoscopy and laser lithotripsy were carried out under sedation, blood pressure increased from 110/50 mmHg to 160/80 mmHg.
Conclusion
These cases show that tetraplegic patients are likely to develop autonomic dysreflexia during cystoscopy and vesical lithotripsy, performed without anaesthesia. Health professionals should educate spinal cord injury patients regarding risks of autonomic dysreflexia, when urological procedures are carried out without anaesthesia. If spinal cord injury patients are made aware of potentially life-threatening complications of autonomic dysreflexia, they are less likely to decline anaesthesia for urological procedures. Subrachnoid block or epidural meperidine blocks nociceptive impulses from urinary bladder and prevents occurrence of autonomic dysreflexia. If spinal cord injury patients with lesions above T-6 decline anaesthesia, nifedipine 10 mg should be given sublingually prior to cystoscopy to prevent increase in blood pressure due to autonomic dysreflexia.
doi:10.1186/1754-9493-6-3
PMCID: PMC3296613  PMID: 22348226
24.  Autonomic dysreflexia in a tetraplegic patient due to a blocked urethral catheter: spinal cord injury patients with lesions above T-6 require prompt treatment of an obstructed urinary catheter to prevent life-threatening complications of autonomic dysreflexia 
Background
The Manchester Triage System is commonly used as the triage system in emergency departments of the UK. As per the Manchester Triage System, patients presenting with retention of urine to the accident and emergency department are categorized to yellow, which denotes that the ideal maximum time to first contact with a treating clinician will be 60 min. Cervical spinal cord injury patients, in whom urinary catheter is blocked, may develop suddenly headache, sweating, high blood pressure, cardiac dysrhythmia, convulsions, intracranial bleed, and acute neurogenic pulmonary oedema as a result of autonomic dysreflexia due to a distended bladder.
Case presentation
A 46-year-old male with C-6 tetraplegia developed urinary retention because of a blocked catheter. He was seen immediately on arrival in the spinal injuries unit. The blocked catheter was removed and a new catheter was about to be inserted. Then this patient said that the ceiling lights were very bright and glaring. Five milligrams of Nifedipine was given sublingually. This patient started having fits involving his head, face, neck and shoulders with loss of consciousness. A 14-French silicone Foley catheter was inserted per urethra without any delay and 300 ml of clear urine was drained. This patient recovered consciousness within 5 min. Computed tomography of the brain revealed no focal cerebral or cerebellar abnormality. There was no intra-cranial haemorrhage.
Conclusion
This case illustrates that spinal cord injury patients with lesion above T-6, who develop retention of urine because of a blocked catheter, may look apparently well, but these patients can develop suddenly life-threatening autonomic dysreflexia. Therefore, spinal cord injury patients, who present to the accident and emergency department or spinal units with a blocked urinary catheter, should be seen urgently although their vital signs may be stable on arrival. Increasing the awareness of staff in emergency departments regarding autonomic dysreflexia as well as education of the patient and carers will be useful in preventing this complication in persons with spinal cord injury.
doi:10.1186/1865-1380-5-6
PMCID: PMC3395851  PMID: 22296914
25.  Fine needle aspiration cytology in fibromatosis 
Fibromatosis form a spectrum of clinicopathologic entities characterized by the infiltrative proliferation of fibroblasts that lack malignant cytologic features. The fibromatosis can be localized or infiltrative and multicentric and can involve internal tissues and organs as the mesentery, retroperitoneum, breast, and almost every organ and region of the body, including the bones, the meninges and the central nervous system. We report a case of 37-year-old male who presented with a right supraclavicular mass with superficial infiltrative type of fibromatosis and fine needle aspiration cytology (FNAC) was performed. We report this case because of limited literature of FNAC in fibromatosis and quick role of FNAC in the diagnosis of fibromatosis.
doi:10.4103/0970-9371.93221
PMCID: PMC3307459  PMID: 22438623
Fibromatosis; fine needle aspiration cytology; soft tissue lesions

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