Introduction and Objectives:

To prospectively document the perioperative complications of percutaneous nephrolithotomy (PCNL) using the modified Clavien grading system. Evaluation of complications and clearance rates according to stone complexity using the validated Guy's Stone Score (GSS) was also done.

Materials and Methods:

A total of 221 renal units underwent 278 PCNL procedures at a urology resident training center between September 2010 and September 2011 and data were recorded prospectively in our registry. Patients with co-morbidities like diabetes, renal failure, hypertension and cardiopulmonary diseases were excluded. Stone complexity was classified according to the GSS while peri-operative complications were recorded using the modified Clavien grading system.

Results:

Two hundred and forty-five complications were encountered in 278 PCNL procedures involving 116 renal units (41.72%). Complications of Grades 1, 2, 3a, 3b, 4a, 4b and 5 were seen in 52 (18.7%), 122 (43.8%), 42 (15.1%), 18 (6.4%), 6 (2.1%), 4 (1.4%) and 1 (0.3%) renal units respectively. There were 68, 98, 50 and 5 renal units in GSS I, II, III and IV groups, respectively. All grades of complications were more common in GSS III and IV (P<0.05). For GSS I, II, III and IV 100%, 74%, 56% and 0% of renal units, respectively, were stone-free after one session and 0%, 24%, 44% and 60% respectively needed two sessions to be stone-free.

Conclusion:

Although the complication rates were higher most were of low grade and self-limiting. Complications were significantly more common with higher GSS and the GSS effectively predicted stone-free rates.

OVO-like proteins (OVOL) are members of the zinc finger protein family and serve as transcription factors to regulate gene expression in various differentiation processes. Recent studies have shown that OVOL genes are involved in epithelial development and differentiation in a wide variety of organisms; yet there is a lack of comprehensive studies that describe OVOL proteins from an evolutionary perspective. Using comparative genomic analysis, we traced three different OVOL genes (OVOL1-3) in vertebrates. One gene, OVOL3, was duplicated during a whole-genome-duplication event in fish, but only the copy (OVOL3b) was retained. From early-branching metazoa to humans, we found that a core domain, comprising a tetrad of C2H2 zinc fingers, is conserved. By domain comparison of the OVOL proteins, we found that they evolved in different metazoan lineages by attaching intrinsically-disordered (ID) segments of N/C-terminal extensions of 100 to 1000 amino acids to this conserved core. These ID regions originated independently across different animal lineages giving rise to different types of OVOL genes over the course of metazoan evolution. We illustrated the molecular evolution of metazoan OVOL genes over a period of 700 million years (MY). This study both extends our current understanding of the structure/function relationship of metazoan OVOL genes, and assembles a good platform for further characterization of OVOL genes from diverged organisms.

Background

Insertions of spliceosomal introns are very rare events during evolution of vertebrates and the mechanisms governing creation of novel intron(s) remain obscure. Largely, gene structures of melanocortin (MC) receptors are characterized by intron-less architecture. However, recently a few exceptions have been reported in some fishes. This warrants a systematic survey of MC receptors for understanding intron insertion events during vertebrate evolution.

Methodology/Principal Findings

We have compiled an extended list of MC receptors from different vertebrate genomes with variations in fishes. Notably, the closely linked MC2Rs and MC5Rs from a group of ray-finned fishes have three and one intron insertion(s), respectively, with conserved positions and intron phase. In both genes, one novel insertion was in the highly conserved DRY motif at the end of helix TM3. Further, the proto-splice site MAG↑R is maintained at intron insertion sites in these two genes. However, the orthologs of these receptors from zebrafish and tetrapods are intron-less, suggesting these introns are simultaneously created in selected fishes. Surprisingly, these novel introns are traceable only in four fish genomes. We found that these fish genomes are severely compacted after the separation from zebrafish. Furthermore, we also report novel intron insertions in P2Y receptors and in CHRM3. Finally, we report ultrasmall introns in MC2R genes from selected fishes.

Conclusions/Significance

The current repository of MC receptors illustrates that fishes have no MC3R ortholog. MC2R, MC5R, P2Y receptors and CHRM3 have novel intron insertions only in ray-finned fishes that underwent genome compaction. These receptors share one intron at an identical position suggestive of being inserted contemporaneously. In addition to repetitive elements, genome compaction is now believed to be a new hallmark that promotes intron insertions, as it requires rapid DNA breakage and subsequent repair processes to gain back normal functionality.

Alternative splicing and posttranslational modifications (PTMs) are major sources of protein diversity in eukaryotic proteomes. The SR protein SF2/ASF is an oncoprotein that functions in pre-mRNA splicing, with additional roles in other posttranscriptional and translational events. Functional studies of SR protein PTMs have focused exclusively on the reversible phosphorylation of Ser residues in the C-terminal RS domain. We confirmed that human SF2/ASF is methylated at residues R93, R97, and R109, which were identified in a global proteomic analysis of Arg methylation, and further investigated whether these methylated residues regulate the properties of SF2/ASF. We show that the three arginines additively control the subcellular localization of SF2/ASF and that both the positive charge and the methylation state are important. Mutations that block methylation and remove the positive charge result in the cytoplasmic accumulation of SF2/ASF. The consequent decrease in nuclear SF2/ASF levels prevents it from modulating the alternative splicing of target genes, results in higher translation stimulation, and abrogates the enhancement of nonsense-mediated mRNA decay. This study addresses the mechanisms by which Arg methylation and the associated positive charge regulate the activities of SF2/ASF and emphasizes the significance of localization control for an oncoprotein with multiple functions in different cellular compartments.

SF2/ASF is a prototypical SR protein, with important roles in splicing and other aspects of mRNA metabolism. SFRS1 (SF2/ASF) is a potent proto-oncogene with abnormal expression in many tumors. We found that SF2/ASF negatively autoregulates its expression to maintain homeostatic levels. We characterized six SF2/ASF alternatively spliced mRNA isoforms: the major isoform encodes full-length protein, whereas the others are either retained in the nucleus or degraded by NMD. Unproductive splicing accounts for only part of the autoregulation, which occurs primarily at the translational level. The effect is specific to SF2/ASF and requires RRM2. The ultraconserved 3′UTR is necessary and sufficient for downregulation. SF2/ASF overexpression shifts the distribution of target mRNA towards mono-ribosomes, and translational repression is partly independent of Dicer and a 5′ cap. Thus, multiple post-transcriptional and translational mechanisms are involved in fine-tuning the expression of SF2/ASF.

We report a unique case of primary hepatocellular carcinoma in an ectopic liver rest in the left renal hilum masquerading as a left adrenal tumor. Adrenal tumors have been reported within adrenal rests inside the liver but hepatocellular carcinoma in ectopic liver rests in the adrenal area is an extremely rare entity. To the best of our knowledge, this is the first case report from the Indian subcontinent to describe this event in the English literature.

Our patient, a sixty-year-old, non-diabetic, non-hypertensive male, presented with a history of left flank pain for the past six months. He was a chronic smoker and also consumed excessive amounts of alcohol. He had chronic obstructive pulmonary disease and was hepatitis B surface antigen positive. A contrast enhanced computer tomography scan of the abdomen showed an 8×8×8 cm, well-defined, heterogeneously enhancing mass with central necrosis, in the left suprarenal region. The provisional diagnosis of an adrenal tumor was made and open transperitoneal excision of the tumor along with two enlarged lymph nodes was done. Immunohistochemistry staining of the specimen revealed it to be a primary hepato cellular carcinoma. The patient died within six months of surgery owing to extensive metastases. We concluded that chronic hepatitis B infection and chronic and excessive alcohol consumption and/or chronic smoking may have been the predisposing factors for the occurrence of primary hepatocellular carcin oma in the liver rest in our patient. The prognosis appears to be poor despite surgical management.

Ureterocystoplasty is a novel operation well suited for patients having small capacity urinary bladder with unilateral poorly functioning kidney and megaureter. The megaureter is detubularized and used for urinary bladder augmentation. The ureter lining has advantage of being non-secretory and free from the metabolic complications of enterocystoplasty. This operation is mainly done in children. This is one of the very few from the Asian subcontinent which describes the short term results of ureterocystoplasty in an adult patient. We report a case wherein ureterocystoplasty was performed in an 18-year male presented with a small capacity neurogenic bladder with a grossly dilated and tortuous left ureter and a non-functioning left kidney. Left ureter was detubularized and used for augmentation after left nephrectomy. Blood supply to the left ureter was preserved during the dissection. After the operation, the bladder capacity increased adequately and he is doing well at a followup of 1 year. Ureterocystoplasty works well in the adult patients also and the bladder capacity increases adequately following this procedure.

Fistula following circumcision and at times accompanied by disfigurement of the glans penis is a common problem in our country, where a large number of circumcision is performed by untrained professionals. These complications may have profound negative psychological impact on the growing child. Herein, we report the successful closure of such fistula using buccal mucosa, which occurred following circumcision (for phimosis) in a 15 year old boy. This resulted in the disfigurement of the glans penis with a distal urethral fistula. The fistula was managed by dorsal onlay buccal mucosa graft urethroplasty (BMGU). The patient has excellent cosmesis at 6 months followup with a good urinary stream. This technique can give better results than those, where skin grafts or local flaps are used for fistula closure. BMGU is a versatile technique with good long term results. The cosmesis and functional results are satisfactory and help in improving the self esteem and sexual function in the years to come.

A rare case of Acute lymphoblastic leukemia with hemophillia in a 12 year old boy is presented in the article. Patient was known case of hemophillia (factor VIII deficiency). He was diagnosed as a case of ALL based on bone marrow examination and immunophenotypic study. Patient was treated as per Children Cancer group guidelines. The main aim of reporting this rare association lies in developing treatment strategies in preventing life threatening bleeding due to this rare association which though may be accidental but need further research.

Chronic prostatitis / chronic pelvic pain syndrome (NIH-type II and type III prostatitis) are common cause of chronic pelvic pain. The exact etiology of these entities are unknown. They are associated with varying degree of voiding and sexual dysfunction. Consensus regarding treatment of these pain syndromes is lacking. Review of literature suggest a therapeutic role of alpha adrenergic receptor blockers in the management of NIH-type II and type III prostatitis. A trial of alpha-blocker is reasonably inexpensive and appropriate for most patients suffering from NIH-type III prostatitis and NIH-type II prostatitis. A general consensus is that if a patient agrees to a trial of alpha-blocker therapy which subsequently shows a good response then it should be continued for at least 6 months for a proper therapeutic effect. This review analyses the role of alpha-blockers in this disease/syndrome; discusses the possible mechanism of action through which these drugs provide relief and also highlights some of the important trials which have paved way for this particular treatment option in this intriguing disease /syndrome.

Background

The purpose of this prospective study was to evaluate the donor site morbidity in patients who have undergone oral mucosa graft urethroplasty for stricture of the urethra. The impact of smoking and oral consumption of tobacco and/or paan masala on the donor site was also assessed. This study is probably the first of its kind where the affect of smoking, paan masala and tobacco chewing on the donor site morbidity has been documented.

Methods

Forty-eight patients suffering from stricture of the urethra underwent oral mucosa graft urethroplasty between July 2005 and December 2007. The patients were divided into two groups (users or non-users) based on tobacco consumption and oral hygiene. The donor site was evaluated at frequent intervals for pain, swelling, numbness, bleeding, salivation and tightness of mouth.

Results

Donor site morbidity was more in users with poor oral hygiene. Pain scores were higher amongst the users and the morbidity persisted longer in the users compared to non-users with good oral hygiene.

Conclusion

Patients who consume tobacco and have poor oral hygiene should be warned regarding poorer outcomes after oral mucosa graft urethroplasty.