Diagnostic utility of GATA3 immunohistochemical expression in urothelial carcinoma

Aims: This study aims to explore the utility of GATA binding protein 3, a zinc finger transcription factor, expression in genitourinary carcinoma, especially urothelial carcinoma. Settings and Design: It is a prospective study where 74 consecutive cases of urothelial carcinoma along with 10 cases each of prostatic adenocarcinoma (PC) and conventional clear cell renal cell carcinoma were included between August 2016 and January 2017. Methods and Materials: All the cases were histopathologically evaluated and immunohistochemically stained for GATA binding protein 3. Only nuclear positivity was considered as positive. Immunoreactivity score for GATA expression was calculated based on the staining intensity as well as percentage. Statistical Analysis Used: The statistical analysis was done using Statistical Package for Social Sciences Version 15.0 statistical analysis software. P value of <0.05 was considered statistically significance. Results: GATA3 expressions were seen in 77% of the cases of urothelial carcinoma, whereas none of the clear cell renal cell carcinoma and prostatic adenocarcinoma cases was GATA3 positive. GATA3 expression significantly correlated with histological grade and muscle invasion with a weaker or negative expression in high-grade muscle invasive tumor as compared to low-grade and noninvasive neoplasm. Significantly weaker expression of GATA3 was found in cases with severe nuclear pleomorphism, mitosis >10/10 hpf, presence of necrosis, and tumor-infiltrating lymphocytes. No significant change in the status of GATA3 expression was seen in follow-up cases between initial Transurethral resection of bladder tumor (TURBT) and post-recurrence TURBT or radical cystectomy specimens. Conclusions: GATA3 as a sensitive and specific marker for urothelial carcinoma can be effectively used to exclude other genitourinary malignancies, PC, and renal cell carcinoma, at metastatic site. This marker can also be effectively used in predicting the probable grade and invasion in biopsy material with poor morphological characteristics, thereby helping in appropriate management in such cases.

Restoring esthetics by immediately loaded implant placement.

The replacement of a single missing anterior tooth with an implant-supported crown is a demanding therapy. This report describes a treatment in which an anterior maxillary implant was immediately restored with a provisional restoration. During the provisional phase, an optimal emergence profile was created by adjusting the provisional restoration. An impression was made with an individually fabricated impression post for an accurate reproduction of the established emergence profile and, finally, a screw-retained all-ceramic crown was placed. By implementing this protocol, an optimal definitive result could be achieved, together with immediate patient satisfaction.

Chronic infections & coronary artery disease with special reference to Chalmydia pneumoniae.

Background & objectives: Studies on cardiovascular diseases (CVD) in India have shown about 10-20 per cent of cases with no obvious risk factors, raising a suspicion of infections as a cause. There is a paucity of data on this possible role of infections. This study was, therefore, undertaken to find out the association between infection due to Chlamydia pneumoniae and other organisms and coronary artery disease (CAD). Methods: Patients with CAD were selected in group I (acute myocardial infarction, AMI) and group III (patients undergoing coronary artery bypass graft (CABG) surgery), and normal controls in group II. Routine biochemical, haematological and inflammatory tests [C-reactive protein (CRP), total leucocyte count (TLC), fibrinogen, ESR], serodiagnostic tests for IgA and IgG antibodies to C. pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), Mycoplasma pneumoniae and Parvovirus B-19 by ELISA kits, C. pneumoniae antigen by microimmunofluorescence and PCR from endothelial tissue obtained at CABG were carried out. Aortic punch biopsies were done in patients who underwent CABG. Results: Acute MI patients had a significantly higher association with accepted cardiac risk factors, lipid profile, inflammatory and thrombogenic tests. IgG and IgA antibodies levels against C. pneumoniae were not significantly different in the controls as against the AMI group. However, C. pneumoniae antigen seropositive group had significant association with HDL cholesterol, lipid tetrad index (P<0.001) and with triglycerides. Parvovirus B antigen was detected in 8.3 per cent of tissue specimens by PCR and of 44 patients with AMI (6.8%) were also positive for parvovirus B-19 IgG antibodies. Interpretation & conclusions: There was no direct evidence of the involvement of C. pneumoniae and other infective agents and viruses in CAD. It is possible that such infections produce an indirect adverse effect on the lipid profile.

Cumulative effect of risk factors on short-term surgical success of mitomycin augmented trabeculectomy.

CONTEXT: Risk factors for failure of trabeculectomy may have a cumulative effect on the outcome. AIMS: To study the effect of preoperative ocular risk factors on the surgical outcome of trabeculectomy augmented with 2 commonly used doses of Mitomycin C. SETTINGS AND DESIGN: In a prospective cohort study, cases were recruited over an 18 month period. 92 eyes of 83 patients with one to three known risk factors for failure of trabeculectomy underwent Mitomycin-C (MMC) augmented trabeculectomy. METHODS AND MATERIAL: Trabeculectomy was done with a randomly chosen MMC dose of 0.2 mg/ml or 0.4 mg/ml. All cases were followed up for a period of at least 3 months. Surgical success was defined as the lowering of intraocular pressure (IOP) below 21 mmHg during the follow up period. STATISTICAL ANALYSIS USED: Chi square test, paired t test, odds ratio, effect size. RESULTS: Eyes with two or three risk factors (out of aphakic glaucoma, failed trabeculectomy, neovascular glaucoma, post uveitic glaucoma, traumatic glaucoma, adherent leucoma, juvenile glaucoma, prolonged medical therapy, steroid induced glaucoma, post penetrating keratoplasty glaucoma and developmental glaucoma) had a significantly poorer surgical success rate (88% and 78%) than eyes with one risk factor (100%). 0.4 mg/ml MMC used sub-sclerally had a statistically similar effect on lowering the IOP as 0.2 mg/ml in all groups. The rate of complications was significantly higher in the 0.4 mg/ml subgroup. CONCLUSIONS: The presence of more than one preoperative ocular risk factor, affects the surgical success of MMC augmented trabeculectomy in high-risk cases. Because of the significantly higher rate of complications with the higher dose of MMC, this should be used sparingly, only in cases with more than two risk factors.

Protein mediated cholesterol absorption in locusts Schistocerca gregaria (Forskal) and Locusta migratoria (Linn).

Absorption and transport of 3H cholesterol from the midgut to hemolymph and other tissues was studied in the locusts Schistocerca gregaria and Locusta migratoria. S. gregaria are able to absorb dietary cholesterol in the midgut and release into the hemolymph in vivo and into the incubation medium in virto. Certain proteins of midgut origin are involved in the absorption and release of cholesterol. The proteins designated as cholesterol binding proteins (CBP's) were fractionated by gel filtration chromatography using Sepharose CL-6B-200 column. Presence of a protein and its binding with cholesterol is confirmed by TCA precipitation after subsequent incubation of midgut in the incubation medium. Cholesterol binding with the proteins was also confirmed in native polyacrylamide gel electrophoresis. Biosynthesis of this protein takes place in the midgut which is inhibited by a protein synthesis inhibitor, cycloheximide. It also inhibits absorption and release of cholesterol from the midgut. The cholesterol binding activity was associated with a peak containing proteins ranging from molecular weights of 17-32 kDa in SDS-PAGE gels. Treatment of midgut with cycloheximide resulted in reduced cholesterol binding activity. Dilipidation of mucin and transport in presence of bile salts yielded a higher cholesterol binding activity. Although the absorption and release of cholesterol was observed in the hemolymph of both sexes, the ovary exhibited higher cholesterol binding as compared to testis.

The trabecular meshwork in acute and chronic angle closure glaucoma.

PURPOSE: To determine the effect of acute and chronic primary angle closure glaucoma (PACG) on the trabecular meshwork. METHODS: Trabecular specimens of 16 consecutive patients with primary angle closure glaucoma (PACG)--6 acute PACG eyes, and 10 chronic PACG eyes without an acute attack--were studied by light and electron microscopy. RESULTS: Acute PACG: The trabecular meshwork revealed a generalised oedema and an accumulation of pigment in the widened trabecular spaces and Schlemm's canal. Attenuated trabecular endothelial cells appeared to be devoid of subcellular components. Chronic PACG: In chronic PACG eyes the trabecular architecture had lost its regular arrangement, with fewer and narrower trabecular spaces and fusion of the trabecular beams in areas. There were numerous electron-dense bodies in the trabecular tissues, both within the trabecular beams and in the extracellular spaces, which had a banded fibrillar structure. An overall loss of endothelial cells was noted; the remaining cells were crowded together and were polymorphic. Melanin pigment was present both within the stroma and in the endothelial cells. CONCLUSIONS: Pigment accumulation in the trabecular spaces and within the cells and a noninflammatory degeneration appeared to be the primary changes in the trabecular meshwork after acute angle closure glaucoma. In chronic PACG eyes, there was evidence of loss of endothelial cells and reactive repair processes. These changes were present in areas away from visible peripheral anterior synechiae. A gonioscopic evaluation of the extent of peripheral anterior synechiae alone may not reflect the extent of trabecular meshwork damage in acute and chronic PACG. Patients experiencing an acute attack of PACG require a long-term follow up, because the intraocular pressure (IOP) may rise later, due to ongoing changes compromising the outflow facility, or due to the effects of aging in the trabecular meshwork.

Inhibitory effect of 1-benzyl-5[(C)-2,6-dimethyl-1,5-heptadienyl] imidazole (KK-42) on desert locust, Schistocerca gregaria forsk.

Imidazole compound KK-42 was tested for its inhibitory effect on Schistocerca gregaria. The compound caused 80% mortality after 19 days of treatment with 100 microg of KK-42/insect. It also caused the production of deformed adults at even lower doses. Ecdysteroid content, when estimated by RIA, declined due to KK-42 treatment in both haemolymph and ovaries of the insect. Reduction in ecdysteroid titer was maximum at 100 microg of KK-42/insect. The value estimated by RIA was 0.34 ng/pL haemolymph as compared to 0.97 ng/microL in case of controls. Similarly,ecdysteroid content of ovaries detected was 0.48 ng/mg in treated ones as compared to 0.61 ng/mg in controls. Histological studies, however, revealed no alteration in the ovarian tissues due to KK-42 treatment.

Assessing the role of subconjunctival versus intrascleral application of mitomycin C in high-risk trabeculectomies.

PURPOSE: To compare the efficacy and safety of subconjunctival and intrascleral applications of mitomycin C (MMC) in trabeculectomy for high-risk glaucomas. METHODOLOGY: A randomized prospective clinical study was conducted on 41 consecutive eyes with a high risk of glaucoma surgery failure. Patients were randomized to trabeculectomy and application of subconjunctival MMC or to trabeculectomy and application of intrascleral MMC. MMC solution 0.2 mg/ml was applied for 3 minutes under the conjunctival flap overlying the proposed site of trabeculectomy in Group I (n=21), or intrasclerally under the superficial scleral flap in Group II (n=20) RESULTS: After a follow-up of one year, the intraocular pressure (IOP) decreased from a mean basal IOP of 33.0 +/- 8.4 mm Hg to 12.56 +/- 2.54 mm Hg in Group I and from 30.9 +/- 6.6 mm Hg to 11.6 +/- 2.21 mm Hg in Group II. The IOP was 6-21 mmHg, without medication, in 90.5 % of the eyes in Group I and 75 % of the eyes Group II. Ocular hypotony, hypotony maculopathy, choroidal detachment and a shallow anterior chamber were more frequent with the intrascleral application of MMC during trabeculectomy, but the difference was not statistically significant. The overall success of the surgery at one year, i.e., achieving an IOP of 6-21 mmHg and a stable vision, (reduction in visual acuity of < or = 2 lines), was 90.5% in Group I and 75 % in Group II. CONCLUSION: No significant difference was seen in overall success or complication between subconjunctival and intrascleral application of MMC-augmented trabeculectomies in glaucomatous eyes at high risk of surgical failure.

Ross procedure in an infant.

The Ross procedure is gaining acceptance as the procedure of choice for aortic valve replacement in children. We present the case of a 4-month-old child (weight 3.2 kg) suffering from congenital valvar aortic stenosis who underwent a Ross procedure. We believe that this is the youngest patient to have undergone this procedure successfully in the Indian subcontinent.

Visual field assessment in glaucoma: comparative evaluation of manual kinetic Goldmann perimetry and automated static perimetry.

PURPOSE: To compare the detection and assessment of progression of visual field defects in primary open-angle glaucoma with manual suprathreshold perimetry on Goldmann perimeter and automated static threshold perimetry on Humphery visual field (HVF) analyzer. METHODS: 105 eyes of 54 patients of primary open-angle glaucoma were followed up with 3-monthly perimetry on Goldmann perimeter and HVF analyzer, for a period of 9 months. RESULTS: HVF analyzer picked up visual field defects in 48 (46%) eyes whereas Goldmann perimeter picked up visual field defects in 26 (25%) eyes. HVF analyzer demonstrated progression in 14 eyes whereas Goldmann perimeter detected progression in 7 eyes during follow up of 9 months. CONCLUSIONS: HVF analyzer is superior to Goldmann perimeter to document and to demonstrate progression of visual field defects in primary open-angle glaucoma.

Contact trans-scleral diode laser cyclophotocoagulation treatment for refractory glaucomas in the Indian population.

PURPOSE: This study aimed to evaluate the clinical efficacy of contact diode trans-scleral cyclophotocoagulation (TSCPC) for treatment of refractory glaucomas. METHOD: Fifty two eyes of 52 patients, (post-penetrating keratoplasty glaucoma: 16 eyes; adherent leucoma with secondary glaucoma: 8 eyes; aphakic glaucoma: 6 eyes; neovascular glaucoma: 6 eyes; narrow angle glaucoma: 6 eyes; and other secondary glaucomas: 10 eyes) were followed up from 3.5-18 months (average 12 months) after TSCPC. The treatment parameters using the contact G probe were--energy: 3-4J; area: 40 spots spread over 360 degrees; site: 1.2-1.5 mm posterior to limbus. Retreatments (22 eyes; 42%) were given whenever intraocular pressure (IOP) exceeded 22 mmHg despite maximum tolerable topical therapy. RESULTS: IOP decreased from a baseline of 44.7 (+/- 7.3) mmHg to 15 (+/- 3.7) mmHg at first week and was 15.2 +/- (8.2) mmHg at the last follow up. Successful control of IOP (< 22 mmHg) occurred in 30 (58%) eyes after a single treatment and in 48 (92%) eyes following retreatment. Complications included reduction in visual acuity from light perception (LP) only to no light perception (NLP) in two eyes and phthisis bulbi in one eye. CONCLUSION: Contact trans-scleral diode laser cyclophotocoagulation is effective in lowering IOP in eyes with intractable glaucoma with few side effects in Indian subjects.

Profile of the subtypes of angle closure glaucoma in a tertiary hospital in north India.

A prospective study of 500 consecutive patients of primary angle closure glaucoma was undertaken to study the clinical profile of the three subtypes: acute, subacute, and chronic. A record of age and sex distributions, symptomatology, the best corrected visual acuity, gonioscopy, visual fields, methods of control of intraocular pressure, and status of the second eye was maintained. Statistical analysis of these parameters and the subtypes of angle closure glaucoma was carried out using the chi-square test. Angle closure glaucoma constituted 45.9% of all primary adult glaucomas seen. 24.8% of these had acute angle closure glaucoma, 31.2% subacute, and 44% chronic glaucoma. Angle closure glaucoma occurred maximally in the sixth decade and females constituted 51.4% of those affected. The difference in symptoms among the subtypes was significant (p < 0.001). More than 80% of the chronic eyes had no significant symptoms. Visual field defects specific for glaucoma were seen in only 15.1% of chronic glaucoma eyes. Bilaterality was commonest in subacute angle closure glaucoma (95.5%) and least in acute angle closure 35.5%. Nd YAG iridotomy alone or with topical medication controlled the intraocular pressure in 48.3% of acute angle closure glaucoma, 78.8% of subacutes, and 30% of chronic eyes. Statistically, each parameter reviewed was significantly different among the subtypes. There are considerable differences as well as an overlap of clinical features in the subtypes of angle closure glaucoma, which suggest some anatomical differences or dissimilar pathogenic mechanisms in these eyes.

Evaluation of efficacy of standard haemodialysis and verapamil added peritoneal dialysis.

The study was carried out on 30 adult subjects of acute renal failure who were randomly divided into two groups of 15 patients each. Group A patients were subjected to standard haemodialysis (HD) for 4 hours using holofibre dialyser and group B patients received 36 hours of peritoneal dialysis (PD) where Verapamil was added intraperitonealy in the dose of 10 mg/ L/cycle in the clearance periods III, V, VII, IX and XI (Total dose 150 mg). The 36 hours of PD consisted of 36 cycles of one hour duration each and these were divided into 12 clearance periods (CP) of 3 cycles each. Following both the forms of dialytic treatments, there was significant improvement in the signs of uraemia with fall in the blood urea and serum creatinine levels. The peritoneal clearances, percentage fall of urea and creatinine, and protein loss were similar in the two groups (p > 0.5). However, ultrafiltration was significantly higher in the group B. No untoward effects were noticed in group B however group A patients had episodes of hypotension (5)] disequilibrium (6) and cardiac arrhythmias (1). It can be concluded that both clinically and biochemically, 36 hours of Verapamil added PD and 4 hours of hemodialysis are comparable and therefore, peritoneal dialysis may be used more frequently in acute renal failure specially in situations where trained dialysis staff is not available and patients are not haemodynamically stable.

A comparative evaluation of pilocarpine 1% and clonidine 0.125% versus timolol 0.5%.

All the presently available antiglaucoma medications have either local or systemic adverse effects. Combinations of drugs are being used not only to increase the effectivity and compliance but also to decrease the incidence and magnitude of side effects. The single dose response of open angle glaucoma eyes to pilocarpine 1%, clonidine 0.125%, a combination of pilocarpine 1% and clonidine 0.125%, and timolol 0.5% was studied in a double blind, masked, cross over study. Over a period of twelve hours the effectivity of the combination of pilocarpine 1% and clonidine 0.125% was significantly more than that of either drug alone and was found to be similar to that of timolol 0.5%. No local or systemic adverse effects were seen.

A modified technique of anterior peribulbar anaesthesia.

A modified technique of peribulbar anaesthesia consisting of a single injection of anaesthetic solution with a 26G, half inch insulin needle was evaluated in 50 eyes. The operative procedures included extracapsular cataract extraction with intraocular lens implantation in 20 eyes, intracapsular lens extraction in 20 eyes, and trabeculectomy in 10 eyes. Complete anaesthesia was obtained in 45 eyes (90%). No significant complications were observed except for mild to moderate conjunctival chemosis in 40 eyes (80%). The technique is easy to learn, safe, effective and relatively economical.