Hepatic Encephalopathy: A Retrospective Analysis

A review of 34 patients was conducted to investigate the causes of hepatic encephalopathy. Hypokalemia, infection, and gastrointestinal tract bleeding were found to be the usual precipitating factors. Women are affected more commonly, and gastrointestinal tract hemorrhage is usually the terminal event.     

Significance of pharmaceutical excipients in prescribed medicines: a case report

Pharmaceutical excipients need careful observation as they play a significant role in treatment outcomes. It is imperative for a physician to collect complete patient profile before prescribing new medications for current treatment. We present a case report on the significance of pharmaceutical excipients in prescribed medicines.     

Single molecule measurements of mechanical interactions within ternary SNARE complexes and dynamics of their disassembly: SNAP25 vs. SNAP23

Regulated exocytosis is a crucial event for intercellular communication between neurons and astrocytes within the CNS. The soluble N -ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex, composed of synaptobrevin 2, syntaxin and synaptosome-associated protein of 25 kDa or 23 kDa (SNAP25 or SNAP23), is essential in this process. It was reported that SNAP25 and SNAP23 have distinct roles in exocytotic release, where SNAP25, but not SNAP23, supports an exocytotic burst. It is not clear, however, whether this is due to the intrinsic properties of the ternary SNARE complex, containing either SNAP25 or SNAP23, or perhaps due to the differential association of these proteins with ancillary proteins to the complex. Here, using force spectroscopy, we show from single molecule investigations of the SNARE complex, that SNAP23A created a local interaction at the ionic layer by cuffing syntaxin 1A and synaptobrevin 2, similar to the action of SNAP25B; thus either of the ternary complexes would allow positioning of vesicles at a maximal distance of ∼13 nm from the plasma membrane. However, the stability of the ternary SNARE complex containing SNAP23A is less than half of that for the complex containing SNAP25B. Thus, differences in the stability of the two different ternary complexes could underlie some of the SNAP25/23 differential ability to control the exocytotic burst.     

Visual prognosis, intraocular pressure control and complications in phacomorphic glaucoma following manual small incision cataract surgery

Aims:

To evaluate intraocular pressure (IOP) control, visual prognosis and complications following manual small incision cataract surgery among eyes with phacomorphic glaucoma.

Materials and Methods:

This prospective, non-randomized interventional consecutive case series included all patients with phacomorphic glaucoma who presented to a tertiary eye care referral center in South India between March 2006 and April 2007. All patients underwent slit-lamp bio-microscopy, applanation tonometry and gonioscopy of the other eye to rule out angle closure. Small incision cataract surgery with intraocular lens implantation was performed in all affected eyes. Complete ophthalmic examination was done at each follow-up visit.

Results:

A total of 74 eyes with phacomorphic glaucoma were included in this study. The preoperative mean IOP was 38.4±14.3 mmHg and mean IOP at last follow-up was 12.7±2.4 mmHg. There was a statistically significant difference between IOP at presentation and IOP at last follow-up (P< 0.001). None of the eyes required long-term antiglaucoma medication. No significant intraoperative complications were noted. The final postoperative best corrected visual acuity was 20/40 or better in 51 patients. Eighteen eyes had corneal edema and 36 eyes had anterior chamber inflammation. Both conditions resolved with standard medical therapy.

Conclusion:

Manual small incision cataract surgery is safe and effective in controlling IOP and achieving good functional visual acuity with minimal complications in the management of phacomorphic glaucoma in developing countries.     

Predictors of Response to Sildenafil Citrate Following Radiation Therapy for Prostate Cancer

IntroductionPhosphodiesterase type 5 inhibitor (PDE5) use is a treatment strategy for prostate cancer patients with post-radiation therapy (RT) erectile dysfunction (ED).AimTo define the predictors of sildenafil response in men treated with RT for prostate cancer.Main Outcome MeasuresInternational Index of Erectile Function (IIEF).MethodsPatients were enrolled prospectively if they met the following criteria: (i) either a three-dimensional conformal external beam (EBRT) or brachytherapy (BT) with or without androgen deprivation (AD) for prostate cancer; (ii) self-reported ability to have sexual intercourse prior to RT; (iii) experienced onset of ED following RT; (iv) candidates for sildenafil citrate use; (v) followed-up periodically; and (vi) completed the IIEF at least 12 months after RT. Failure to respond to sildenafil was defined as IIEF-erectile function (EF) domain score of <22.ResultsOne hundred fifty-two patients met all the criteria: 110 in the EBRT group and 42 in the BT group. Mean age was 62 years. The mean follow-up was 38 months. Mean radiation dose for EBRT was 78 Gy and for BT was 101 Gy. Thirty-five patients received AD, 25% of EBRT, and 62% of BT patients. Sixty-one percent of the patients receiving AD had exposure only pre-RT, whereas 39% had pre- and post-RT AD exposure. The mean duration of AD was 4.6 months. Post-RT IIEF-EF domain score at >24 months was 17. Successful response to sildenafil occurred in 68% of men at 12 months after RT, 50% at 24 months, and 36% at 36 months. On multivariable analysis, predictors of failure to respond to sildenafil were: older age, longer time after RT, AD > 4 months duration, and RT dose > 85 Gy. Modality of radiation delivery was not predictive of sildenafil failure.ConclusionsA steady decrease in sildenafil response was seen with increasing duration after RT. Several factors were predictive of sildenafil failure. Teloken PE, Parker M, Mohideen N, and Mulhall JP. Predictors of response to sildenafil citrate following radiation therapy for prostate cancer. J Sex Med **;**:**–**.     

The effect of intracoronary infusion of bone marrow‐derived mononuclear cells on all‐cause mortality in acute myocardial infarction: rationale and design of the BAMI trial

Over the past 13 years bone marrow‐derived mononuclear cells (BM‐MNCs) have been widely investigated for clinical efficacy in patients following acute myocardial infarction (AMI). These early phase II trials have used various surrogate markers to judge efficacy and, although promising, the results have been inconsistent. The phase III BAMI trial has therefore been designed to demonstrate that intracoronary infusion of BM‐MNCs is safe and will significantly reduce the time to first occurrence of all‐cause death in patients with reduced left ventricular ejection fraction after successful reperfusion for ST‐elevation AMI (powered with the aim of detecting a 25% reduction in all‐cause mortality). This is a multinational, multicentre, randomized, open‐label, controlled, parallel‐group phase III study aiming to enrol approximately 3000 patients in 11 European countries with at least 17 sites. Eligible patients who have impaired left ventricular ejection (≤45%) following successful reperfusion for AMI will be randomized to treatment or control group in a 1:1 ratio. The treatment group will receive intracoronary infusion of BM‐MNCs 2–8 days after successful reperfusion for AMI added on top of optimal standard of care. The control group will receive optimal standard of care. The primary endpoint is time from randomization to all‐cause death. The BAMI trial is pivotal and the largest trial to date of BM‐MNCs in patients with impaired left ventricular function following AMI. The aim of the trial is to provide a definitive answer as to whether BM‐MNCs reduce all‐cause mortality in this group of patients.     

Etiology and epidemiological analysis of glaucoma-filtering bleb infections in a tertiary eye care hospital in South India

Purpose:

To evaluate the microbial etiology and associated risk factors among patients with blebitis following trabeculectomy.

Materials and Methods:

A retrospective analysis of all culture-proven blebitis was performed in patients who underwent trabeculectomy between January 2004 and December 2008. A standardized form was filled out for each patient, documenting sociodemographic features and information pertaining to risk factors. Swabbing of the infected bleb surface was performed for all suspected cases and further subjected to microbiological analysis.

Results:

A total of 23 patients with culture-proven blebitis were treated during the study period, with a mean age of 59.2 years (59.2 ± SD: 12.8; range, 30-81 years). Duration of onset was early (≤36 months) in six (26%) cases and late (> 36 months) in 17 (74%) cases with a range between 15 and 144 months (mean, 82.91 months; SD: 41.89). All 23 blebs were located superiorly and of which, 21 (91%) were microcystic avascular, 1 (4%) diffuse avascular, and 1 (4%) vascular flattened. The predominant risk factor identified was bleb leak (35%; 8 of 23) followed by thin bleb (22%; 5 of 23) and blepharitis (17%; 4 of 23). Bleb leaks (100%) were recorded only in patients with late onset (≥ 9 years) of infection (P< 0.001), while the incidence of ocular surface disease (100%) occurred early (≤3 years) (P< 0.001). Use of topical steroids was associated frequently with cases of thin blebs (80%; 4 of 5) (P< 0.001), while topical antibiotics showed bleb leaks (88%; 7 of 8) (P< 0.001). Coagulase-positive staphylococci were frequently recovered from blebitis with thin blebs (71%; 5 of 7) (P = 0.001), Coagulase-negative staphylococci (CoNS) with bleb leak (100%; 8 of 8) (P< 0.001), Corynebacterium with blepharitis (100%; 3 of 3) (P = 0.001), and Streptococci with releasable sutures (75%; 3 of 4) (P = 0.001).

Conclusion

Bleb leak is the principal risk factor responsible for late-onset blebitis, while early-onset blebitis could be ascribed to ocular surface diseases. Streptococci were mainly responsible for early onset of infection, while the late onset was due to CoNS.     

Engineering colloidally stable,highly fluorescent and nontoxic Cu nanoclusters via reaction parameter optimization

Metal nanoclusters (NCs) composed of the least number of atoms (a few to tens) have become very attractive for their emerging properties owing to their ultrasmall size. Preparing copper nanoclusters (Cu NCs) in an aqueous medium with high emission properties, strong colloidal stability, and low toxicity has been a long-standing challenge. Although Cu NCs are earth-abundant and inexpensive, they have been comparatively less explored due to their various limitations, such as ease of surface oxidation, poor colloidal stability, and high toxicity. To overcome these constraints, we established a facile synthetic route by optimizing the reaction parameters, especially altering the effective concentration of the reducing agent, to influence their optical characteristics. The improvement of the photoluminescence intensity and superior colloidal stability was modeled from a theoretical standpoint. Moreover, the as-synthesized Cu NCs showed a significant reduction of toxicity in both in vitro and in vivo models. The possibility of using such Cu NCs as a diagnostic probe toward C. elegans was explored. Also, the extension of our approach toward improving the photoluminescence intensity of the Cu NCs on other ligand systems was demonstrated.

A facile synthetic strategy to engineer improved fluorescent quantum yield, colloidally stable, and low toxic Cu nanoclusters is introduced. These nanoclusters have the potential to be used as excellent bioimaging probes.