Cancer/testis antigens as molecular drug targets using network pharmacology.

Present chemotherapeutic drugs have limited efficacy and severe side effects. Considering the complexity of cancer, an effective strategy is necessary to discover multiple new drug targets. Cancer/testis antigens are vital for cancer cell progression. We have performed a computational network analysis of cancer/testis antigens and assessed these antigens as drug targets. During this analysis, protein interaction network of 700 human CT antigens was investigated. CT antigen network consisted of eight independent components. Four major hubs and two minor hubs were identified that play nodal role in the flow of information across the largest network. We have predicted 30 potential drug targets by analysing several topological parameters such as betweenness centrality, cluster coefficient and probable protein complexes. Structural and functional roles of potential drug targets have also been anatomized. Analysis of the CT antigen network enables us to pinpoint a set of candidate proteins that if targeted could be detrimental for cancerous cell without affecting any normal cell. The list of putative proteins is a starting point for experimental validation and may help further in the discovery of new anticancer drug targets.

Dynamics of ultrafine particles inside a roadway tunnel.

Size-segregated ultrafine particles from motor vehicles were investigated in the Craeybeckx tunnel (E19 motorway, Antwerp, Belgium) at two measurement sites, at 100 and 300 m inside the tunnel, respectively, during March 2008. It was observed that out of the three size modes, nucleation, Aitken, and accumulation, Aitken mode was the most dominant size fraction inside the tunnel. The diurnal variation in ultrafine particle (UFP) levels closely follows the vehicular traffic inside the tunnel, which was maximum during office rush hours, both in the morning and evening and minimum during night-time around 3 am. The tunnel data showed very high growth rates in comparison with free atmosphere. The average condensation sink during the growth period was 14.1-17.3 × 10(-2) s(-1). The average growth rate (GR) of geometric mean diameter was found to be 18.6 ± 2.45 nm h(-1). It was observed that increase in Aitken mode was related to the numbers of heavy-duty vehicles (HDV), as they emit mainly in the Aitken mode. The higher Aitken mode during traffic jams correlated well with HDV numbers. At the end of the tunnel, sudden dilution leading to fast coagulation was responsible for the sudden drop in the UFP number concentration.

Disparity in cholecalciferol content of commercial preparations available in India.

BACKGROUND: High prevalence of vitamin D deficiency (VDD) has been reported throughout the India for all age groups. Increased awareness about VDD among treating physicians has led to increased prescriptions of vitamin D preparations. Based on our experience of varied clinical and radiological response with different vitamin D formulations, we decided to assess cholecalciferol content of commonly available vitamin D formulations. MATERIALS AND METHODS: We measured cholecalciferol content of 14 commercial preparations (two in the form of tablets and 12 as sachet) available in Indian market. Lab analysis was carried out in Shriram Institute for Industrial Research by high-performance liquid chromatography. RESULTS: Of the total 14 samples analyzed only 4 (28.57%) were found to be within the acceptable ranges from -90 to +125% as defined by Indian Pharmacopia while 5 (35.7%) had higher and 5 (35.7%) had lower than the acceptable range. The percentage variation in cholecalciferol content as observed from the printed ranged widely from -91% to +65%. CONCLUSIONS: Our study shows a high degree of variability in cholecalciferol content of commercial preparations available in the Indian pharmaceutical market. This variation has many clinical implications as it may lead both, under treatment as well as vitamin D toxicity.

A-90 Day Gavage Safety Assessment of Boswellia serrata in Rats.

The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of digestive system, respiratory ailments and bone related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt.

Xanthoma of the urinary bladder - A rare entity.

Xanthomas of the urinary bladder are rare. They may be associated with metabolic disorders. We hereby report a case of bladder xanthoma.

A randomized controlled trial to study the effect of IV hydration on the duration of labor in nulliparous women.

PURPOSE: To compare the effects of two different regimens of intravenous hydration and oral hydration on the duration of active labor. METHODS: Two hundred and ninety-three low risk term primigravida in active labor were randomized into three groups. The first group had 99 patients who received oral fluids only, the second group of 98 patients received intravenous Ringer lactate at the rate of 125 ml/h (IV 125 ml) and the third group had 96 patients who received intravenous Ringer lactate at a rate of 250 ml/h (IV 250 ml). Amniotomy and oxytocin administration were allowed according to the physician's discretion. RESULTS: The mean duration of labor in the oral fluid group was 391, 363 min in the 125 ml/h group and 343 min in the 250 ml/h group, P = 0.203. The incidence of prolonged labor more than 12 h in the oral fluid group was 7.1% in the oral fluid group, 4.1% in the 125 ml/h group and 3.1% in the 250 ml/h group, P = 0.402. The oxytocin requirement was 37% in the oral group, 32% in the 125 ml/h group and 33% in the 250 ml/h group, P = 0.68. There was a statistically significant reduction in the incidence of vomiting in patients receiving intravenous hydration, i.e. 24.2% in the oral group, 11.2% in the 125 ml/h group and 6.3% in the 250 ml/h group, P = 0.001. There was no difference in the mode of delivery, maternal or neonatal complications between the three groups. CONCLUSION: This study establishes a trend towards decreased incidence of prolonged labor and less vomiting in patients receiving intravenous hydration.

Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis jiroveci infection in orthotopic liver transplantation.

We report a patient who presented 6 months after orthotopic liver transplantation (OLT) with fever, dyspnea, and pulmonary infiltrates with biopsy-confirmed Pneumocystis jiroveci infection associated with a process of bronchiolitis obliterans organizing pneumonia (BOOP). We present this second case of BOOP associated with P. carinii pneumonia after OLT to highlight the risk of such disease combination in all transplant patients as well as discuss the protective effect of post-transplant prednisolone with trimethoprim-sulfamethoxazole prophylaxis and the possible duration of prophylaxis.

A cost comparison of open versus percutaneous approaches to management of large staghorn calculi.

AIM: This paper compares the cost of open versus percutaneous approaches to the management of large staghorn calculi in a tertiary care hospital in India. MATERIALS AND METHODS: Patients who underwent surgery for staghorn calculi larger than 6 cm between January 1998 and December 2003 were included. Those who had confounding factors in terms of cost such as additional surgical or medical procedures and complications unrelated to the surgery were excluded. The process of costing was done by following the clinical pathway. RESULTS: There were 13 patients who had open stone surgery and 19 patients who underwent percutaneous nephrolithotripsy (PCNL). The major differences in cost were seen in the higher cost of instruments and consumables in the PCNL group. The cost of management of complications widened this gap. Two patients in the PCNL group and none in the residual group required redo surgery. The residual stones in the open and PCNL groups required a mean of 2525 and 3623 shocks per patient respectively. Complete clearance after redo surgery and Shockwave lithotripsy (SWL) was seen in 92% and 58% in the open and PCNL arms respectively. The overall cost per patient was $625 per PCNL and $499 per open surgery. The final mean residual stone size in the PCNL group was 4.84 mm whereas it was 0.38 mm in the open group. The effective cost of achieving complete clearance in one patient was $1078 in the PCNL group and $543 in the open group. CONCLUSION: Open stone surgery is less costly than PCNL in large staghorn calculi.

Endobronchial Tuberculosis Simulating Lung Cancer and Healing without Bronchial Stenosis.

Endobroncheal tuberculosis is defined as tuberculous infection of the tracheobronchial tree with microbial and histopathological evidence. The disease is usually mistaken for other lung diseases including lung cancer. Bronchial stenosis is a common complication of this type of tuberculosis despite the use of effective anti-tuberculous chemotherapy. We are presenting a case of endobronchial tuberculosis that simulated lung cancer and healed without residual bronchial stenosis.

Shock wave lithotripsy in solitary functioning kidneys: is prophylactic stenting necessary?

OBJECTIVE: To assess the safety of shock wave lithotripsy (SWL) without prophylactic stents in solitary functioning kidneys. PATIENTS AND METHODS: Sixteen solitary functioning kidneys with 23 renal stones with a size of <15 mm were treated with SWL as the primary modality. All patients were counseled about the possibility of obstruction, and treatment was offered to those who consented. The safety of SWL was assessed by the need for interventions and the posttreatment renal function. RESULTS: In 14 patients lithotripsy was uneventful. The duration of treatment ranged from 5 to 35 days. One patient with a 15-mm pelvic calculus presented with anuria which resolved before intervention. In 1 patient fragmentation failed, and percutaneous nephrolithotomy was performed. CONCLUSIONS: In solitary functioning kidneys, SWL is safe without prophylactic stents in properly selected and closely monitored patients. Avoiding stents decreases costs, duration of treatment, and stent-related morbidity without unduly compromising safety.

Bladder-sparing surgery in locally advanced nonurological pelvic malignancy.

INTRODUCTION: The urinary bladder is commonly involved in pelvic malignancy. The incidence of apparent extension into adjacent organs in locally advanced colorectal malignancy is 5-12%. It is not known with other pelvic malignancy. No guidelines are available for its management. Often a dilemma exists between cystectomy and a bladder-sparing procedure. We studied the validity of bladder-sparing surgery (BSS) in locally advanced nonurological pelvic malignancy. METHODS: Hospital records of patients who underwent BSS along with other surgeries (abdomino-perineal resection, anterior resection, anterior exenteration, debulking surgery and total pelvic exenteration) from January 1992 to May 2003 were reviewed. RESULTS: BSS was done in 15 patients. 10 had locally advanced colorectal malignancy, 3 with soft tissue masses of the lateral pelvic wall, 1 had ovarian malignancy and the other had residual mass following radiotherapy and chemotherapy of cancer cervix. In those with locally advanced colorectal malignancy, symptoms suggestive of lower urinary tract involvement were present in 8 (80%). Urine examination and ultrasonography was not helpful in suggesting bladder involvement, unlike CT scan of abdomen and pelvis. Preoperative cystoscopy showed endoscopic evidence of bladder involvement in 7 (87.5%). Bladder was involved supratrigonally in 7. Partial cystectomy was done in 9 patients. The left ureter was involved in 6 patients, and they required ureteric reimplantation. Palliative transurethral resection was done in 1 patient with tumor infiltration at the bladder neck and prostate. 50% patients had bothersome lower urinary tract symptoms at 1 year. One patient died in the immediate postoperative period due to a nonurological cause. Overall 3-year survival rate was 40%. CONCLUSION: Unlike primary bladder cancers these lesions are not multifocal and hence en block conservative bladder-sparing surgery can be offered. Preoperative CT scan or MRI can predict lower urinary tract involvement and help in decision-making by both surgeon and patient. The ultimate decision for bladder sparing is based on intraoperative findings. Sparing the bladder might provide better quality of life by avoiding urinary diversion without altering survival.

Tubercular ureteric strictures.

OBJECTIVE: To review the presentation of tubercular ureteric strictures and assesses the role of balloon dilatation and open surgical repair in their management. METHODS: This was a retrospective review of tubercular ureteric strictures managed between January 1993 and December 2002. The records were analyzed to assess clinical presentation and compare the results of balloon dilatation with open surgical repair. Success was defined as adequate drainage on imaging, no worsening of renal function, no recurrence of symptoms and no requirement of intervention on further follow up. The long term success rates were compared using the t-test for proportion. RESULTS: Of 73 strictures, 88% had lower urinary tract symptoms. Genital abnormalities suggestive of tuberculosis was observed in 40% male patients. Urine examination yielded aseptic pyuria in 85%, positive AFB smears in 36% and positive AFB cultures in 32%. A small capacity bladder and non-functioning renal units were the only consistent findings on intravenous urogram. Nephrectomy was performed in 37% cases due to non salvageable kidneys at presentation. The success rate of stenting fell from 93% on immediate follow up to 59% on a follow-up of 12 months. At 90% success rates on a follow-up of 7 months open surgical repair was superior (p 0.03). Long term success following balloon dilatation in renal units with good function was 78% compared to 25% for poorly functioning units. (p= 0.01) CONCLUSION: Open surgical repair is superior to balloon dilatation in the management of tubercular ureteric strictures. Renal function may predict the success of balloon dilatation.

Erectile dysfunction.

With phosphodiesterase inhibitors, a safe and effective oral therapy has emerged for erectile dysfunction. Increasing awareness, particularly through the media, is inducing more men to seek help for this condition. Erectile dysfunction is defined as the persistent inability to achieve or maintain an erection adequate for satisfactory sexual activity. The prevalence increases with age. Basic and clinical research is identifying the neurovascular and humoral control of the mechanisms. The initial evaluation should differentiate erectile dysfunction from premature ejaculation and loss of libido. Myocardial insufficiency, hypogonadism and peripheral neuropathy should be looked for. Initial laboratory investigations should be restricted to identifying previously undetected medical illness that may directly contribute to erectile dysfunction. Discussing the available options with the couple is an important aspect. If erectile dysfunction is secondary to other treatable disorders these should be treated simultaneously. When other diseases that require intervention are ruled out and if there are no contraindications, therapy may be initiated with a phosphodiesterase inhibitor. In selected cases, psychosexual therapy may be beneficial. If phosphodiesterase inhibitors are contraindicated, vacuum constriction devices may be tried. Further options include intracavemosal injection, intraurethral instillation, penile revascularization and prosthesis. The availability of effective and well-tolerated oral medications has dramatically changed the clinical approach to erectile dysfunction. Pharmacotherapy is the preferred cost-effective first-line therapy in the vast majority of patients. A stepped-care approach is followed in the primary care and family practice settings. Appropriate urological, endocrine and psychiatric referrals, and shared decision-making with the couple will enable effective treatment of men with erectile dysfunction.

Does failure to visualize the ureter distal to an impacted calculus constitute an impediment to successful lithotripsy?

BACKGROUND: A severe degree of ureteral obstruction is viewed as a predictor of poor outcome in shockwave lithotripsy (SWL). Impacted stones are often considered a contraindication to in-situ SWL. PATIENTS AND METHODS: Impaction in our study was defined as failure to visualize the ureter distal to the calculus with proximal hold-up of contrast for as long as 3 hours on an intravenous urogram (IVU). We evaluated 30 patients with impacted ureteral calculi, who were compared with a second unimpacted group matched for stone size and stone location. The calculi were reorganized into < or =10-mm and >10-mm groups. The results were compared in terms of clearance rates, number of shockwaves, number of sessions, and number of days between the start of SWL and clearance. RESULTS: Between January 1998 and December 2001, 30 impacted stones were treated with lithotripsy. Complete clearance rates in the impacted as well as the non-impacted group were 76.7%. There was no statistical difference in the number of shockwaves, sessions, or time to clearance. The results were poorer in lower-ureteral than upper-ureteral calculi, but this difference did not reach statistical significance. However, the differences between the < or =10-mm and >10-mm stones were statistically significant. CONCLUSION: Impaction on an IVU does not affect the results of lithotripsy.

GB virus C/hepatitis G virus and TT virus infections among high risk renal transplant recipients in India.

BACKGROUND: GB virus C/hepatitis G virus (GBV-C/HGV) and TT virus (TTV) have been widely reported in patients with high parenteral risk such as haemodialysis and renal transplant recipients. The occurrence of these agents in association with hepatitis B virus (HBV) and hepatitis C virus (HCV), in Indian renal transplant recipients, is yet unreported. STUDY DESIGN: Molecular and serological markers of GBV-C/HGV and TTV were examined in addition to those for HBV, HCV and hepatitis D virus (HDV) in a selected group of seventy renal transplant recipients. HGV RNA detection was achieved using primers specific for the 5'NCR and NS5a regions of the genome. Anti-GBV-C/HGV antibody was detected using the mu plate anti-HG env kit (Roche, Germany). TTV DNA PCR was performed using primers specific for the coding region (method A) of the genome. In 50% of patients, TTV DNA was also tested for using primers specific for the non-coding region (method B). Host related factors such as age, alanine aminotransferase (ALT) levels, number of transfusions, haemodialysis sessions, and months following transplantation were also studied. RESULTS: Exposure rates to GBV-C/HGV, TTV (method A), HBV, HCV and HDV were 58.6, 32.9, 52.9, 54.3 and 2.9%, respectively. 'Active' infection as measured by viraemia and/or virus-specific antigenaemia for GBV-C/HGV, TTV, HBV and HCV was 52.9, 32.9, 15.7 and 52.9%, respectively. The majority of GBV-C/HGV and TTV infections were seen as co-infections with other hepatitis viruses. Single infection with GBV-C/HGV and TTV was seen in ten (14.2%) and eight (11.4%) patients, and was not associated with ALT elevation when compared to uninfected blood donors. Using univariate analysis, GBV-C/HGV RNA was significantly associated with > or =20 haemodialysis sessions. TTV DNA occurrence was not associated with any risk factors. CONCLUSIONS: There is a high occurrence of GBV-C/HGV and TTV in this select group of renal transplant recipients in India. These viruses mostly occurred in the context of co-infections with other hepatitis viruses. Long term effects of multiple hepatotropic viral infections need to be carefully documented in such transplant populations.

Paediatric renal transplantation--a 15 year experience.

OBJECTIVE: To review the outcome of paediatric renal transplantation over a period of 15 years in a developing country. METHODS: This is a retrospective study of 63 children, less than 15 years of age, who underwent living-related renal transplantation in Christian Medical College and Hospital Vellore between 1984 and 1996. RESULTS: The records of 12 patients were not adequate for detailed analysis. Parents were the donors for these children in 84.3% of cases. The most common known cause of end-stage renal disease in these children was reflux nephropathy. Combinations of cyclosporine, azathioprine and prednisolone were used as immunosuppressive drugs. Complications occurred in 16 patients. During the follow-up period, eight patients died and two returned to receiving haemodialysis. Patient survival was 92% at the end of 1 year and 90% at the end of 3 years. Graft survival was 88% and 86% at 1 and 3 years, respectively. CONCLUSION: Our study validates the concept of renal transplantation as optimal therapy with adequate medical, social and functional rehabilitation for children with end-stage renal disease. Our study also indicates that vesicoureteric reflux appears to be underdiagnosed and should be actively pursued to prevent complications.

Transurethral prostatic resection or laser therapy for men with acute urinary retention: the ClasP randomized trial.

PURPOSE: Transurethral resection of the prostate is the standard operation for acute urinary retention, although laser prostatectomy is reportedly effective and safe. The ClasP (conservative management, laser, transurethral resection of the prostate) study compared transurethral prostatic resection and noncontact neodymium (Nd):YAG visual laser assisted prostatectomy for treatment of acute urinary retention. MATERIALS AND METHODS: This study was a multicenter randomized controlled trial, analyses were by intention to treat and followup was at 7.5 months after randomization. Primary outcomes were treatment failure, and included International Prostate Symptom Score, International Prostate Symptom Score quality of life score, residual urine and flow rate. Secondary outcomes included complications, and duration of catheterization and hospitalization. RESULTS: A total of 148 men were randomized to transurethral prostatic resection (74) and laser (74). There were fewer treatment failures after prostatic resection (p = 0.008) and fewer men after resection required secondary surgery for poor results (1 versus 7, p = 0.029). Maximum flow rates after transurethral prostatic resection were better than after laser (mean difference 4.4 ml. per second). Comparison of symptom and quality of life scores demonstrated that any clinically significant advantage for laser could be ruled out. Patients stayed a mean of 2 extra days in the hospital after resection. The duration of catheterization was greater after laser but significantly fewer major treatment complications were found with laser therapy. CONCLUSIONS: Transurethral prostatic resection was more effective, resulted in fewer failures than laser treatment and remains the procedure of choice for men with acute urinary retention.

A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study.

PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.