Review and update of involuntary facial movement disorders presenting in the ophthalmological setting

We review the existing literature on the involuntary facial movement disorders—benign essential blepharospasm, apraxia of eyelid opening, hemifacial spasm, and aberrant facial nerve regeneration. The etiology of idiopathic blepharospasm, a disorder of the central nervous system, and hemifacial spasm, a condition involving the facial nerve of the peripheral nervous system, is markedly different. We discuss established methods of managing patients and highlight new approaches.     

Aberrant promoter methylation of p16 in colorectal adenocarcinoma in North Indian patients

AIM: To investigate p16 gene methylation and its expression in 30 patients with sporadic colorectal adenocarcinoma in a North Indian population.METHODS: Methylation specific polymerase chain reaction was used to detect p16 gene methylation and immunohistochemistry was used to study the p16 expression in 30 sporadic colorectal tumors as well as adjoining and normal tissue specimens.RESULTS: Aberrant promoter methylation of p16 gene was detected in 12 (40%) tumor specimens, whereas no promoter methylation was observed in adjoining and normal tissue. Immunohistochemistry showed expression of p16 protein in 26 (86.6%) colorectal tumors whereas complete loss of expression was seen in 4 (13.3%) and reduced expression was observed in 12 (40%) tumors. In the adjoining mucosa, expression of p16 was in 11 (36.6%) whereas no clear positivity for p16 protein was seen in normal tissue. There was a significant difference in the expression of p16 protein in tumor tissue and adjoining mucosa (P < 0.001). The methylation of the p16 gene had a significant effect on the expression of p16 protein (P = 0.021). There was a significant association of methylation of p16 gene with the tumor size (P = 0.015) and of the loss/reduced expression of p16 protein with the proximal site of the tumor (P = 0.047). Promoter methylation and expression of p16 had no relation with the survival of the patients (P > 0.05).CONCLUSION: Our study demonstrated that promoter hypermethylation of the p16 gene results in loss/reduced expression of p16 protein and this loss/reduced expression may contribute to tumor enlargement.     

Association of Technetium99m MAG-3 renal scintigraphy with change in creatinine clearance following chemoradiation to the abdomen in patients with gastrointestinal malignancies

Background

Information on differential renal function following abdominal chemoradiation is limited. This study evaluated the association between renal function as measured by biochemical endpoints and scintigraphy and dose volume parameters in patients with gastrointestinal malignancies.

Materials and methods

Patients who received abdominal chemoradiation between 2002 and 2009 were identified for this study. Technetium^99m MAG-3 scintigraphy and laboratory data were obtained prior to and after chemoradiation in 6 month intervals. Factors assessed included age, gender, hypertension, diabetes, and dose volume parameters. Renal function was assessed by biochemical endpoints and renal scintigraphy.

Results

Significant reductions in relative renal function of the primarily irradiated kidney and creatinine clearance were seen. Split renal function decreased from 49.75% pre-radiation to 47.74% and 41.28% at 6-12 months and >12 months post-radiation (P=0.0184). Creatinine clearance declined from 90.67ml/min pre-radiation to 82.23ml/min and 74.54ml/min at 6-12 months and >12 months post-radiation (P<0.0001). Univariate analysis of patients who had at least one post-radiation renogram showed the percent volumes of the primarily irradiated kidney receiving ≥ 25 Gy (V₂₅) and 40 Gy (V₄₀) were significantly associated with ≥5% decrease in relative renal function (P=0.0387 and P=0.0438 respectively).

Conclusion

Decline in split renal function using Technetium^99m MAG-3 scintigraphy correlates with decrease in creatinine clearance and radiation dose-volume parameters following abdominal chemoradiation. Change in split perfusion can be detected as early as 6 months post-radiation. Scintigraphy may provide early determination and quantification of subclinical renal injury prior to clinical evidence of nephropathy.     

Macro-aggregates (MAA) of albumin for lung imaging. Studies on better tissue to background ratio, on MAA stability and reuse after its first preparation

The present study was designed to develop stable and economically competitive radioactive technetium-99m macro-aggregates of albumin ((99m)Tc-MAA) which could be used for imaging of lungs. Macro-aggregates were freshly prepared and labeled with (99m)Tc pertechnetate by following the standard protocol which included incubation of formulation at 80(o) C for 10 min. We studied 7 rats in every experiment. The rats were injected intravenously with (99m)Tc MAA and were sacrificed after 10 min to study its distribution in the lungs and other non target tissues using gamma ray spectrometer. This standard protocol was further experimented upon in order to achieve high target to non target ratio. Different formulations were prepared by incubating them at 80 degrees for different incubation times of 5, 10, 15, 20, 25 and 30 min. Formulation of MAA prepared by incubating at 80 degrees for 20 min labeled with (99m)Tc showed the highest target to non target ratio. Another group of rats that received the above formulation were sacrificed after two additional time intervals of 5 and 15 min. The target to non target ratio was high in animals sacrificed after 5 min of injecting them with (99m)Tc the MAA formulation prepared by heating at 80 degrees for 20 min as compared to animals sacrificed after 10 and 15 min. Formulations of MAA following storage at room temperatures which varied from 5(o)C to 18(o)C, for different time durations 1, 2 and 9 days were also evaluated for their ability to be reused after reheating and labeling with (99m)Tc. The formulation of MAA kept for 9 days showed the best target to non-target ratio. The present study suggests that MAA once prepared can be reused following labeling with (99m)Tc even after 9 days of storage with better target to non target ratio as compared to storage timer period of 1 and 2 days.     

Pancreas transplantation: The Wake Forest experience in the new millennium

AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression.METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide.RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a “type 2 diabetes” phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.CONCLUSION: In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.     

Eligibility of persons who inject drugs for treatment of hepatitis C virus infection

In this decade, an increase is expected in end-stage liver disease and hepatocellular carcinoma, most com-monly caused by hepatitis C virus(HCV) infection. Although people who inject drugs(PWID) are the ma-jor source for HCV infection, they were excluded from antiviral treatments until recently. Nowadays there is incontrovertible evidence in favor of treating these pa-tients, and substitution therapy and active substance use are no longer contraindications for antiviral treat-ment. The viral clearance in PWID after HCV antiviral treatment with interferon or pegylated interferon com-bined with ribavirin is comparable to the viral clearance in non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are ad-vised, and their treatment should be considered on an individualized basis. To prevent the spread of HCV in the PWID community, recent active PWID are eligible for treatment in combination with needle exchangeprograms and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treat-ment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID as-sessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strate-gies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detect-ing HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evi-dence concerning HCV infection and treatment strate-gies in PWID.