Immune mechanisms in type-2 diabetic retinopathy.

OBJECTIVE: To enumerate CDR+CD25+ Treg cells and determine serum IL-6 and IL-17 in type 2 diabetes mellitus patients with retinopathy. METHODS: The case-control study was conducted at the Department of Immunology, University of Health Sciences, Lahore, from November 2009 to January 2012 and comprised diabetic patients and healthy controls who were divided into three groups. Group 1 had controls, while Group 2 had diabetic patients without retinopathy and Group 3 had diabetic patients with retinopathy. Flowcytometre and enzyme-linked immunosorbent assay were used for CD4+CD25+ Tregs and serum IL-6 and IL-17 respectively. SPSS 20 was used for statistical analysis. RESULTS: Of the 212 subjects in the study, 30(14%) were Group 1, 30(14%) in Group 2 and 152(72%) in Group 3.There were 25 (83%) women in Group 2 and 101 (66%) in Group 3 compared to 9 (30%) in Group 1. Higher mean age was in Group 3 (50.88 ± 8.9 years) and Group 2 (49.46 ± 9.94 years) compared to Group 1 (34.66 ± 8.78 years) while longer mean disease duration was in Group 3 (10.51 ± 5.24 years) than Group 2 (7.76 ± 4.14 years). Highest median ratio of IL- 6 was in Group 1 (1468.62) (Q1-Q3: 1229.9-1543.35), followed by Group 2 (1455.32) (Q1-Q3:1214.22-158.9) and Group 3 (469.84) (Q1-Q3: 206.53-1231.33) whereas IL-17 was the highest in Group 1 (339.38) (QT-Q3: 159.89- 1174.93), followed by Group 3 (216.60) (Q1-Q3:141.87-410.25) and Group 2 (174.17) (Q1-Q3: 138.77-458.17). Higher percentage of Tregs was in Group 2 (3.07 ± 0.43) followed by Group 1 (2.91 ± 0.04) and Group 3 (2.88 ± 0.38). Significant difference was observed in gender, age, disease duration, level of IL-6 and IL-17 (p < 0.05 each), while no difference was found in glycated haemoglobin, CD4+CD25+ and Tregs (p > 0.05 each). CONCLUSION: Age, gender and duration of diabetes contributed to diabetic retinopathy, while CD4+CD25+ T cells and Treg cells did not. Serum IL-6 and IL-17 were inversely associated with diabetic retinopathy.

Enumeration of CD4(+)CD25(+)T regulatory cells in Type-II diabetes retinopathy.

Diabetes mellitus (DM) is a health concern because it leads to complications such as retinopathy. Pakistan has 6.9 million DM affected people that will be doubled by 2025. A study was designed to enumerate CD4(+)CD25(+)Treg cells in Pakistani type 2 diabetes mellitus (T2DM) patients. It was a cross-sectional case-control study that included 212 subjects. The subjects having diabetic retinopathy were labeled as Group-I (30 healthy volunteers without diabetes), Group-II (30 T2DM patients without retinopathy) and Group-III (152 T2DM patients with retinopathy). The percentage of CD4+CD25+ Treg cells was determined by Flowcytometry. Comparison of CD4(+)CD25(+)T cells among different groups was not significant and higher percentage of Treg cells was observed in Group-II (3.07%) compared to Group-III (2.88%). Age, gender and duration of diabetes may contribute while percentage of CD4(+)CD25(+)T cells and Treg cells were not associated with the development of DR in T2DM.

Inverse relationship of serum IL-17 with type-II diabetes retinopathy.

BACKGROUND: Diabetes mellitus (DM) is a health concern because it leads to complications such as retinopathy. Pakistan has 6.9 million DM affected people that will double by 2025. A study was designed to determine the level of IL-17 in the serum of Pakistani type 2 diabetes mellitus (T2DM) patients. METHODS: It was a cross-sectional case-control study that included 212 subjects. Subjects without diabetes were labeled as Group-I (30 healthy volunteers), Group-II (30 T2DM without retinopathy), and Group-III (152 T2DM with retinopathy). The serum level of IL-17 was determined by ELISA technique. Data was analysed using SPSS 17.0 and one way ANOVA to observe group mean differences. RESULTS: More females were in Group-II (83%) and Group-III (66%) compared to Group-I (30%). The age of subjects was higher in Group-III (50 years) and Group-II (49 years) compared to Group-I (34 years). Group-III had longer mean duration of disease (10.51 years) than Group-II (7.76 years). Group-I had increased levels of IL-17 followed by Group-II and Group-III. On comparison, statistically significant differences were observed among the three groups, and between Group-I and Group-III, but there was no significant difference between Group-I and Group-II, nor between Group-II and Group-III. Further, on comparison of age, gender, and duration of disease there were significant differences while there was no significant difference between the percentages of HbA1c. CONCLUSIONS: Age, gender, and duration of diabetes may contribute in the development of T2DM retinopathy while serum level of IL-17 was inversely associated with T2DM and retinopathy.

Examining sleep, fatigue, and daytime sleepiness in pediatric multiple sclerosis patients.

BACKGROUND: About 2-5% of patients with multiple sclerosis (MS) experience their first symptoms before age 18. Sleep disorders occur frequently in MS. The prevalence of sleep problems and their impact on fatigue and daytime sleepiness in pediatric MS is unknown. OBJECTIVE: To determine whether pediatric MS patients have more sleep disturbances, fatigue, and daytime sleepiness compared with an age-, sex-, and race-matched control group. METHODS: Patients and age-, sex-, and race-matched controls were surveyed to quantify daytime sleepiness via the modified Epworth Sleepiness Scale, sleep quality and hygiene through the Adolescent Sleep Wake and Hygiene Scale, respectively, and fatigue using the PediatricQL Multidimensional Fatigue Scale. RESULTS: Pediatric MS patients (n = 30) and age-, sex-, and race-matched controls (n = 52) had similar levels of fatigue; however, when compared with previously published historical controls, both groups reported worse fatigue across all dimensions (p < 0.05). Pediatric MS patients also had similar sleep quality compared with the matched controls, but reported better sleep hygiene on the 'sleep stability' dimension (p < 0.05). In addition, pediatric MS patients had less daytime sleepiness than the matched controls (p < 0.05). CONCLUSION: Although patients with MS reported similar levels of fatigue, they have better sleep hygiene, which could possibly account for the decreased amount of excessive daytime sleepiness. Also, when compared with historical controls, the MS and control samples reported more fatigue. Thus, caution must be taken when using published control data, especially when not properly matched.

N-Acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a major source of blindness caused by a large variety of mutations that lead to the death of rod photoreceptors. After rods die, cones gradually die from progressive oxidative damage. Several types of antioxidant formulations have been shown to reduce cone cell death over a relatively short-time frame, but in order for this strategy to be translated into a new treatment for patients with RP, prolonged effects will be needed. In this study, we determined that orally administered N-acetylcysteine (NAC) reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1(+/+) and rd10(+/+) mice. In rd10(+/+) mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Topical application of NAC to the cornea also reduced superoxide radicals in the retina and promoted survival and functioning of cones. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, it is reasonable to consider clinical trials to evaluate the effects of prolonged treatment with NAC in patients with RP.

Objective Quantification of Image Quality and Optical Scatter Before and After Nd:YAG Capsulotomy Using a Double-Pass Technique.

PURPOSE: The purpose of this study is to evaluate and compare the correlation between changes in vision and HD Analyzer dual-pass metrics versus changes in vision and conventional subjective slit lamp gradings in pseudophakic patients with posterior capsular opacity undergoing neodymium:yttrium-aluminum-garnet (Nd:YAG) capsulotomy. PATIENTS AND METHODS: High contrast (HC) and low contrast (LC) best spectacle-corrected distance visual acuity (BCVA) and HD Analyzer evaluation were prospectively performed on patients with mild-to-moderate posterior capsular opacification (PCO) and monofocal and accommodating intraocular lens implants. Differences between pre- and post-operative measurements were calculated, along with the correlation of HD Analyzer metrics and slit lamp grading to changes in visual acuity. RESULTS: Following Nd:YAG capsulotomy (n=29), there was statistically significant improvement in HC-BCVA and LC-BCVA, decrease in optical scatter, and corresponding improvement in Strehl ratio and HD Analyzer values at all contrast levels tested (p≤0.05). Pearson test showed a high correlation between the improvement in HC-BCVA (r coefficient = 0.78) and LC-BCVA (r coefficient = 0.71) to the improvement in Objective Scatter Index (OSI). There was a higher correlation of change in HC-BCVA to pre-op OSI  (r2=0.61) than to the subjective PCO grading score (r2 = 0.19). There was also a higher correlation of change in LC-BCVA to pre-op OSI (r2 = 0.49) than to subjective grading (r2 = 0.16). CONCLUSION: The HD Analyzer provides objective measurements of forward light scatter (ie, light directed towards the retina) that can assist with both PCO grading and prediction of improvement of visual quality after YAG laser capsulotomy with higher accuracy than conventional slit lamp assessment based upon backscatter (ie, light traveling to the observer) in patients tested with monofocal and accommodating intraocular lens implants.

Sites and kinetics of donor thrombopoiesis following transplantation of whole bone marrow and progenitor subsets.

INTRODUCTION: Little is known about the sites and kinetics of thrombopoiesis following bone marrow transplant. The spleen is a site of hematopoiesis in a healthy mouse, and hematopoietic activity increases in response to stress. We hypothesized that the spleen is a major site of early post-transplant thrombopoiesis. METHODS: We transplanted whole bone marrow (WBM) or lineage depleted progenitor subsets fractionated based on expression of c-kit and Sca-1 from transgenic mice expressing green fluorescent protein into lethally irradiated C57BL/6 recipients. We also transplanted whole bone marrow cells into healthy and splenectomized mice. Post-transplant megakaryopoiesis was assessed by measuring circulating platelet number, percent donor-derived platelets, bone marrow cellularity, splenic weight, megakaryocyte size, and megakaryocyte concentration from hour 3 to day 28 post transplant. RESULTS: Following transplant, circulating donor-derived platelets were derived only from c-kit expressing subsets. Donor-derived platelets first appeared on post-transplant day five. Splenectomy reduced the number of these earliest circulating platelets. Splenic megakaryopoiesis increased dramatically from day 7-14 post-transplant. However, splenectomy accelerated platelet engraftment during this time frame. CONCLUSION: Overall, these results demonstrate that the first platelets are produced by c-kit expressing megakaryocyte progenitors in the bone marrow and spleen. After post-transplant day 5, the net effect of the spleen on thrombopoiesis is to slow engraftment due to immune effects or hypersplenism.

An eight-year study report on arsenic contamination in groundwater and health effects in Eruani village, Bangladesh and an approach for its mitigation.

Based on several surveys during 1997-2005 and visits of a medical team to Eruani village, Laksham upazila, Comilla district, Bangladesh, the arsenic contamination situation and consequent clinical manifestations of arsenicosis among the villagers, including dermatology, neuropathy, and obstetric outcome, are reported here. Analysis of biological samples from patients and non-patients showed high body burden of arsenic. Even after eight years of known exposure, village children were still drinking arsenic-contaminated water, and many of them had arsenical skin lesions. There were social problems due to the symptoms of arsenicosis. The last survey established that there is a lack of proper awareness among villagers about different aspects of arsenic toxicity. The viability of different options of safe water, such as dugwells, deep tubewells, rainwater harvesting, and surface water with watershed management in the village, was studied. Finally, based on 19 years of field experience, it was felt that, for any successful mitigation programme, emphasis should be given to creating awareness among villagers about the arsenic problem, role of arsenic-free water, better nutrition from local fruits and vegetables, and, above all, active participation of women along with others in the struggle against the arsenic menace.

Negative association of serum IL-6 and IL-17 with type-II diabetes retinopathy.

BACKGROUND: Diabetes mellitus (DM) is a health concern which leads to complications such as retinopathy. Pakistan has 6.9 million people living with DM and this toll will be doubled by 2025. OBJECTIVE: To determine serum IL-6 and IL-17 of type 2 diabetes mellitus (T2DM) patients with retinopathy. METHODS: In this cross-sectional case-control study, 212 subjects enrolled which were categorized into 3 groups. Group-I included 30 subjects without diabetes, group-II consisted of 30 subjects with T2DM without retinopathy and group-III consisted of 152 subjects with T2DM and retinopathy. Serum IL-6 and IL-17 levels were determined by ELISA. Data was analysed using SPSS 17.0 and one way ANOVA to observe group mean differences. RESULTS: Longer mean duration of disease was detected in group-III than group-II (p=0.007). Highest IL-6 level was detected in group-II and highest IL-17 level was detected in group-I. For IL-6, significant differences were detected among groups in total, between Group-I and Group-III and between Group-II and Group-III (p<0.0001 each). Regarding IL-17, significant differences were found among groups in total (p=0.002) and between Group-I and Group-III (p=0.001). No significant difference in the percentages of HbA1c observed between groups. CONCLUSIONS: Age, gender and duration of diabetes contribute to T2DM retinopathy. Serum IL-6 and IL-17 were inversely associated with T2DM retinopathy.

Does lesioning surgery have a role in the management of multietiological tremor in the era of Deep Brain Stimulation?

INTRODUCTION: Surgical management of tremor has evolved over the years with Deep Brain Stimulation (DBS) gradually supplanting lesioning as the mainstay in treatment. In this article, the largest of its kind from our country, we present our experience in the use of lesioning in the management of patients with multietiological tremors. These include not only common indications like Parkinson disease and essential tremor but also rare causes such as Pantothenate kinase associated neurodegeneration (PKAN), multiple sclerosis (MS) and Wilson disease. MATERIALS AND METHODS: Patients with medically refractory tremor who underwent surgery were included in the analysis. A comprehensive clinical and radiological evaluation was performed which was repeated 3 months postoperatively and at successive visits. Video documentation of was obtained at all visits. RESULTS: A total of 21 patients (18 men, 3 women) with an average age 37.7 years (range 21-65 years) underwent stereotactic thalamotomy/subthalamotomy at our institute between 2008 and 2013, for the treatment of medically refractory tremor of varying etiologies. The mean preoperative duration of symptoms was 11 years (range 10 months to 34 years). The median time to onset of improvement was 2 months (range 1 week to 8 months). Analyzing the improvement on the modified FTM scale, in part 1 the scores improved from 21.7 to 1.5, the part II subset improved from an average of 9.2 to 3.2 while the part III subset improved from an average of 14.1 to 4.1 postoperatively. This implied an excellent response in tremor while the other 2 components had a very good response. DISCUSSION: In this study we have for the first time objectively analyzed the tremor improvement with a modified FTM scale and have produced excellent results. We have also shown that tremor of various etiologies respond extremely well to lesioning surgery. While DBS continues to remain the treatment of choice in various types of bilateral tremor, lesioning is very successful in a carefully selected cohort of patients. We are of the opinion that in predominantly unilateral tremor or when the patient cannot afford DBS especially in a country like ours, lesioning surgery is an important tool in the armamentarium of the functional neurosurgeon.

Intrinsic and extrinsic effects of mafG deficiency on hematopoietic recovery following bone marrow transplant.

OBJECTIVE: MafG is the small subunit of the transcription factor NF-E2 that controls terminal megakaryocyte maturation and platelet release. Studies were conducted to evaluate the intrinsic and extrinsic effects of mafG deficiency on bone marrow engraftment kinetics. MATERIALS AND METHODS: We used mafG knockout mice either as donors or recipients in bone marrow transplantations with wild-type mice and compared the engraftment kinetics to transplantations using wild-type donors and recipients. We measured peripheral cell counts, the presence of circulating donor-derived cells by flow cytometry, changes in the cellularity of the bone marrow and splenic weight on day 5, 7, 14, and 1 month post-transplantation. RESULTS: Compared to wild-type recipients, mafG recipients had delayed platelet and leukocyte recovery and lower spleen weight at early time points after transplantation. Intrinsic effects: When mafG-deficient bone marrow served as donor source, we observed more rapid recovery of bone marrow cellularity and increased splenic hematopoiesis. The finding of increased short-term hematopoietic stem cells and progenitors in the mafG-deficient bone marrow could explain the accelerated hematopoietic recovery after transplantation. Furthermore, the expression of Bach 2, which can form a heterodimer with mafG protein, was found to be greatly reduced, while Notch 1 expression was increased in mafG-deficient mice. Extrinsic effects: When mafG-deficient mice were transplant recipients, there were delays in recovery of normal levels of marrow and splenic hematopoiesis as well as circulating leukocytes and platelets. CONCLUSIONS: Our study demonstrates that mafG expression has intrinsic and extrinsic effects on hematopoietic engraftment following bone marrow transplantation.