The Combination Therapy of Oral Steroids and Nerve Decompression for Ulnar Neuritis in Leprosy - Usefulness in Prevention of Progression of Hand Deformities

Hand, being an important functional part of the body, needs healthy complementing motor and sensory nerve supply. Both these functions get compromised following involvement of ulnar nerve in leprosy, which is the commonest nerve involved in Hansen’s disease. It is commonly involved at the elbow level and results in clawing of the hand. There are two routine management protocols viz medical and surgical to manage ulnar nerve damage in leprosy. Steroid therapy along with anti-leprosy regimen is the common medical approach for treatment for ulnar neuritis. Patients not improving with medical management are taken up for surgical decompression. However, when to switch from medical to surgical intervention is topic of debate. In this study we have given steroid therapy in early (4-6 weeks) duration of ulnar neuritis along with anti-leprosy drugs and attempted to determine an appropriate period of medical treatment, beyond which there is no significant benefit in continuing sole medical management if no response is seen. Of the 247 eligible patients, 210 did not respond to 12 months of steroid therapy – the results 193 such patients, treated with steroids and nerve decompression and which were available for follow up were analysed. A total 158/193 (81.8%) cases showed the sensory recovery for touch within 4-6 weeks, deep sensation of pin prick returned in 117/193 (60.62%) cases in 6-8 weeks. Motor recovery was slow, it took 24 to 54 weeks. While 117/193 (60.62%) cases showed improved motor function, in 58/193(30%) cases there was no change and only 18/193(9.3%) cases deteriorated. It appears that period of 12 weeks is an ample time for medical treatment to start showing any form of improvement (motor or sensory) and if there is no improvement, patient should be considered for surgical decompression along with continuation of medical management (Steroid therapy). Our study shows that cases who failed to respond to exclusive medical steroid therapy by 12 weeks responded to combined medical plus surgical treatment as surgical decompression helps in the release of pressure on nerve tissue and improves the functional status.

Cellular mesenchymal epithelial transition (C-MET) gene copy number variation in gastric adenocarcinoma: A pilot search for new marker for targeted therapy in HER-2/neu resistance

Increasing HER-2/neu resistance in gastric carcinoma has encouraged search for new biomarkers for targeted therapy. Cellular mesenchymal epithelial transition (C-MET) is one such tyrosine kinase inhibitor proposed for personalized salvage treatment. We determined frequency of C-MET gene copy number variation (CNV) by Fluorescent in-situ hybridization (FISH) in gastric adenocarcinoma (GAC) and sought its correlation with conventional clinicopathologic parameters. Dual-coloured FISH was done on 32 GAC cases. C-MET gene and centromere 7 signals were counted under fluorescent microscope and ratio was calculated for each case. Correlation between C-MET CNV and conventional clinic-pathologic parameters was done by Fischer exact test. CNV was identified in the form of amplification and polysomy (3.1% each) and associated with poorer prognostic parameters. Our pilot study highlights limited subset of patients that may benefit from anti-C-MET-targeted therapy and thus could be a novel biomarker for targeted intervention in GAC.

Comparative study of alloimmunization against red cell antigens in sickle cell disease & thalassaemia major patients on regular red cell transfusion

Background & objectives: Sickle cell disease (SCD) patients require red cell transfusion during different clinical complications of the disease. Such patients are at a high risk for developing alloantibody against red cell antigens. From India, there are limited data available on alloantibody formation in multiply transfused SCD patients. The present study was thus undertaken to fill up this lacunae by looking at the development of red cell alloantibodies in SCD and ?-thalassaemia patients on regular transfusion. Methods: All sickle cell disease patients undergoing red cell transfusion between 2008 and 2016, were included. During this period, a large number of ?-thalassaemia major patients also underwent regular red cell transfusion. These thalassaemia patients were also included to compare the tendency of antibody formation between SCD and ?-thalassaemia major patients. All patients before regular transfusion were regularly assessed for the development of red cell antibody. Red cell antigen, antibody screen crossmatch and antibody identification were done using the standard technique. Results: A total of 138 patients with SCD aged between 4 and 53 yr (mean 17.6 yr) consisting of 83 males and 55 females (male:female, 1.5:1) along with 333 transfusion-dependent ?-thalassaemia patients were studied. Over the last eight years, 15 patients with SCD and four patients with thalassaemia developed alloantibody (P <0.001). Antibody specificity of their alloantibodies was against Rhc, RhE, Kell, Fya and Fyb only. Sickle cell disease patients with and without alloantibody required on the average 11.8 and 8.6 units of red cell concentrate, respectively (P <0.05). Interpretation & conclusions: About 11 per cent of the transfused sickle cells patients developed alloantibodies. The antibody specificity was restricted to Rh, Kell and Duffy blood group systems. Extended antigen matching involving Rh, Kell and Duffy antigens may prevent alloantibody in such patients.

Retropupillary fixation of iris‑claw lens in visual rehabilitation of aphakic eyes.

Context: Surgical outcome of retropupillary fixation of iris claw lens. Aims: To evaluate the various indications, intra and post‑operative complications, and visual outcome of retropupillary fixation of iris claw lens in aphakic eyes. Settings and Design: The study design is a retrospective study at a tertiary eye care center. Methods: Review of medical records of 61 aphakic eyes of 61 patients, who were rehabilitated with retropupillary fixation of an iris claw lens, with a follow‑up duration of at least 1 year. Statistical Analysis Used: Data analysis was performed using paired t‑test and Chi‑square test. Results: Mean preoperative uncorrected visual acuity was 1.66 ± 0.3 LogMAR and postoperative acuity at 1 year was 0.53 ± 0.5 LogMAR (P = 0.00001). Preoperative distant best‑corrected visual acuity was 0.30 ± 0.48 LogMAR and postoperative acuity at 1 year was 0.27 ± 0.46 LogMAR (P = 0.07). Mean preoperative astigmatism was 1.43 ± 1.94 D and postoperatively was 1.85 ± 2.16 D (P = 0.0127). Mean endothelial cell count was 2353.52 ± 614 cells/mm² preoperatively which decreased to 2200 ± 728 cells/mm² at 1 year follow‑up (P = 0.006). There was no significant difference in central macular thickness and intraocular pressure pre and post-surgery. Complications included ovalization of pupil in 9.83%, hypotony in 1.63%, toxic anterior segment syndrome in 1.63%, cystoid macular edema in 11.47%, epiretinal membrane in 3.27%, and iris atrophy in 6.55%. Conclusion: Iris claw is a safe and an effective method of rehabilitating aphakic eyes.

Impression of Financial Measures in HR Analytics.

In today‟s competitive world, business is all about investments and revenues. Every function of business can be calculated in numbers, then why should HR be left behind. The paper explains how financial measures help the HR mangers to justify every investment made to human resource project. The gap has been filled with the help of HR analytics which transform the raw HR data into insightful information with help of financial measures. HR analytics designed with financial measures helps the Senior HR management to quantify the value of human resources which justifies the investments backing up with the hard reliable evidence. Financial measures along with HR analytics help the HR management to produce net benefits gained from the initiative. This paper gives the overview on how financial measures aids the HR managers to justify the investments made on the human resource projects.

Effect of extreme conditions of Antarctica on human leukocyte antigen-G in Indian expeditioners.

Background & objectives: Immune activation and inflammation play critical roles in the stressful environmental conditions like high altitude, extreme cold, etc. Human leukocyte antigen-G (HLA-G) is a non classical major histocompatiblity complex class I (MHC class- I) protein, upregulated in the context of transplantation, malignancy and inflammation. We hypothesized serum HLA-G as a possible stress biomarker and studied levels of soluble form of HLA-G (sHLA-G) in Indian Antarctic expeditioners. Methods: sHLA-G ELISA was performed in the serum of summer (n=27) and winter (n=22) Indian Antarctic expeditioners. The summer expeditioners were evaluated at three different time points, i.e. before leaving India, after one month ship borne journey, and after staying one month at Indian research base, Maitri in Antarctica, while winter expeditioners were evaluated at five different time points, i.e. before leaving India, and in the month of March, May, August and November at Antarctica. Results: one month ship borne journey did not cause any significant change in the sHLA-G level as compared to the baseline level of the summer expeditioners. sHLA-G levels were not changed significantly in the months of March, May, August and November as compared to the baseline level of the winter expeditioners. Interpretation & conclusions: Our results indicated that the extreme conditions of Antarctica did not cause any significant change in the sHLA-G level in both summer and winter expeditioners.

Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation.

BACKGROUND & OBJECTIVES: C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity of methotrexate (MTX). We studied the relationship between the C677T gene polymorphism and toxicity and efficacy of MTX in patients with rheumatoid arthritis (RA) on folate supplementation. METHODS: A total of 150 RA patients fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/- 20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction enzyme method. Primary endpoint for treatment efficacy was change in disease activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood count, renal and liver function tests and a standardized questionnaire. RESULTS: The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic acid supplementation. Forty two per cent (63/150) of the patients had C677T polymorphism of which 4 were homozygous (T/T) and 59 were heterozygous (C/T). The baseline characteristics of the patients with or without polymorphism were comparable. The frequency of adverse events was not increased in patients with C677T polymorphism with 11 patients experiencing adverse events as compared to 19 in the group without polymorphism (of whom 4 and 7 patients respectively discontinued treatment). The C677T polymorphism was not associated with any difference in response to treatment. INTERPRETATION & CONCLUSION: Our findings suggest that C677T polymorphism in the MTHFR gene is not predictive of toxicity or efficacy of MTX treatment in RA patients receiving folate supplementation. Further studies need to be done to look at polymorphisms in other enzymes that may have association with MTX clinical efficacy and toxicity.

Hereditary coagulation factor X deficiency.

Stuart Prower factor (Factor X) deficiency is a rare hereditary autosomal recessive coagulation disorder. We have come across three cases in the course of last 20 years at our institute. These patients presented with prolonged bleeding after minor trauma, epistaxis, subcutaneous bluish black nodules and two of them presented with history of consanguinity in parents. Hematological findings in correlation with clinical manifestations revealed severe factor X deficiency.

Potential of radiosensitizing agents in cancer chemo-radiotherapy.

Potential of herbs and other plant-based formulations have been increasingly recognized in prevention and treatment of human diseases including cancer. There exist enormous prospect for screening and evaluation of herbal/plant products for developing effective radiosensitization and radioprotection relevant to nuclear research program. Investigations in our laboratory have focused on the mechanism of activity of variety of anticancer and antioxidant agents, namely, Eugenol, (EU), Ellagic acid (EA), Triphala (TPL), Tocopherol Succinate (TOS) and Arachidonic acid on normal and cancer cells with view to design effective protocols in practical radioprotection and cancer radiotherapy. This paper is mainly focused on studies on cytotoxic effects on cancer cell lines. Results have shown that these agents produced radiosensitizing action involving oxidative damage, membrane alteration and damage to nucleic acid in various human cell lines. Studies were performed employing fluorescence probes and electron spin resonance methods and gel electrophoresis protocols. It has been found that cytotoxic effect was induced by initiating membrane oxidative damage and by triggering intracellular generation of reactive oxygen species (ROS) by gamma radiation in combination with phytochemicals like TPL, EA and TOS in tumor cell line Ehrlich Ascites (EAC), Human cervical (HeLa) and breast (MCF-7) cells. Membrane damage and ROS generation was measured by DPH and DCF-FDA fluorescent probes respectively after exposure to low to moderate doses of gamma radiation. This talk will present the cytotoxic effects of phytochemicals in combination with ionizing radiation. It is emphasized that modulation of membrane peroxidative damage and intra cellular ROS may help achieve efficient killing of cancer cells which may provide a new approach to developing effective treatment of cancer.

Programmed cell death as a prognostic indicator for radiation therapy in cervical carcinoma patients: a pilot study.

PURPOSE: In clinical practice, radiation therapy often fails in cervical carcinoma stage IIIB and there is a need to develop a predictive assay for prognosis of radiation treatment outcome in cancer patient. We have attempted to evaluate the relevance of changes in Membrane Fluidity (MF) and associated apoptotic cell death in cervical cancer cells after first fractionated dose of radiation therapy to treatment outcome of stage IIIB cervical carcinoma patients. MATERIALS AND METHODS: Biopsies of 15 patients with histologically proven cervix cancer were collected from the patients before and 24 h after first fractionated radiation dose of 2 grays (Gy). Cell suspension made in Dulbecco's Modified Eagle's Medium (DMEM) were used for further investigations and cell suspension of cervix cancer patient were used to measure MF by fluorescence polarization method and apoptotic index (AI) was determined by Tdt dUTP Nucleotide End Labeling (TUNEL) assay. RESULTS: A substantial increase in MF and AI was observed in cervical cancer cells irradiated ex vivo . A significant correlation ( P P > 0.1) was detected between changes in MF and treatment outcome of patients. CONCLUSION: Preliminary results showed significant change in MF and a marked increase in percentage apoptosis of cervix cancer cells irradiated ex vivo . The changes in AI after first fractionated dose of radiotherapy in cervical carcinoma patients may provide a predictor of prognosis for radiotherapy in uterine cervical carcinoma patients.

Randomized control trial of quinine and artesunate in complicated malaria.

OBJECTIVE: To study the comparative efficacy of the quinine and artesunate in complicated malaria in children. METHODS: All cases admitted to the Pediatrics ward of our hospital with clinical features of complicated malaria (WHO criteria) having asexual forms of P. falciparum in the peripheral smear, were included in the study. Relevant investigations were carried out for confirmation of diagnosis and to assess the prognosis. The patients were sub-grouped into 6 categories as per clinical presentations and each subgroup received alternatively either quinine or artesunate by systematic random sample method. Every odd number received quinine (Group-1) and every even number received artesunate (Group-2). 40 cases in each group were considered for the study and the data obtained were compiled and analyzed by suitable statistical tests. RESULTS: 80 children with complicated malaria enrolled in the present study, of which 48 were boys and 32 were girls. The mean age was 7.93+3.56 years. The most common presentations were fever, splenomegaly and altered sensorium. The CRT, FCT and PCT were significantly less in the artesunate group (50.4 +/- 31.49 hrs; 43.55 +/- 20.12 hrs, and 41.67 +/- 16.78 hrs respectively) as compared to the quinine group (70.15 +/- 17.56 hrs, 62.23 +/- 16.99 hrs, and 52.24 +/- 12.69 hrs respectively) ( p<0.05) No side effects were observed in the artesunate treated group. CONCLUSION: Artesunate is a much better drug than quinine in complicated malaria in terms of rapid coma resolution, fever clearance, parasite clearance and better tolerability.

Electron microscopic studies of the corpuscles of Stannius of an airbreathing teleost (Heteropneustes fossilis).

The ultrastructure of the corpuscles of Stannius (CS) of Heteropneustes fossilis reveals a homogenous cellular composition characterized by only one cell type, with large secretory granules and abundant ribosomal endoplasmic reticulum. These cells are comparable to the type 1 cell described in the CS of other teleosts; type 2 cells, whose presence is ubiquitous in the CS of freshwater species are absent in H. fossilis. Our data on the CS of H. fossilis demonstrate that not all freshwater species possess type 2 cells in their CS and these are not essential for life in freshwater

UreC PCR based diagnosis of Helicobacter pylori infection and detection of cag A gene in gastric biopsies.

Polymerase chain reaction assay using ureC gene specific primers for the detection of Helicobacter pylori in gastric biopsy specimens from 116 dyspeptic patients was compared with other routine invasive diagnostic methods (culture, rapid urease test [RUT] and histology). In parallel, gastric biospy specimens from 54 patients and their corresponding Helicobacter pylori isolates were subjected to PCR with cagA targeting primers using standard protocols. Helicobacter pylori were detected in 53%, 43%, 48% and 50% of patients by PCR, RUT, culture and histological examination respectively. Based on histology and culture positive and at least three test positive result, 44 (37%), 46 (39%) and 26 (22%), and 56 (48%), 52 (44%) and 8 (6%) patients were classified as Helicobacter pylori positive, negative and indeterminate respectively. The sensitivity and specificity of PCR assay was the highest-95% and 100% when compared with both culture and histology positive, and at least any three positive results respectively. The result of cagA positivity in 54 gastric biopsy specimens and their corresponding Helicobacter pylori isolates were identical; 18 of 20 (90%) duodenal ulcer patients and 23 of 28 (82%) patients with chronic gastritis and 2 (40%) of 5 patients with portal hypertension and one gastric biopsy specimens from gastric cancer patients were found to be cagA positive. PCR-based method to detect Helicobacter pylori and the virulence gene cag A directly from gastric biopsy specimens appears to be promising and can curtail the lengthy process of culture-based approaches. The procedure proved to be rapid and reliable and could be utilized for diagnostic purposes.

Comparison of various conventional methods with a polymerase chain reaction assay for detecting methicillin-resistant & susceptible Staphylococcus aureus strains.

BACKGROUND & OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA), a major nosocomial pathogen world-wide, is often difficult to detect due to the heterogeneous nature of expression of oxacillin resistance. In the present study, various conventional methods were compared with polymerase chain reaction on 106 clinical isolates of Staph. aureus for detection of oxacillin resistance. METHODS: A total of 106 clinical isolates of Staph. aureus were tested for oxacillin resistance by disc diffusion, screen agar plates (3 micrograms and 6 micrograms/ml of oxacillin), oxacillin broth (3 micrograms/ml) and mecA based PCR. RESULTS: PCR detected mecA gene amplified product of 604 bp in 57 strains. Disc diffusion failed to detect 7 mecA positive strains but identified 5 mecA negative strains as oxacillin resistant. Screen agar 3 micrograms, screen agar 6 micrograms and oxacillin broth 3 micrograms detected 55, 53 and 55 respectively of the 57 mecA positive strains; however, they also falsely identified 5, 3 and 3 strains of mecA negative strains respectively as oxacillin resistant. The sensitivity, specificity and accuracy of disc diffusion, 3 micrograms screen agar, 6 micrograms screen agar and 3 micrograms oxacillin broth against PCR as gold standard were as follows: 87.7, 89.9 and 88.7 per cent; 96.5, 89.8 and 93.4 per cent; 93.0, 93.9 and 93.4 per cent; 96.5, 93.9 and 95.3 per cent respectively. INTERPRETATION & CONCLUSIONS: The present study demonstrated that disc diffusion test was least reliable and 3 micrograms broth had the highest sensitivity and specificity when compared with PCR for detection of oxacillin resistance. Because of variations among the methods, a combination of tests should be used for the accurate detection of MRSA till new guidelines by an appropriate body are formulated.

Bone marrow necrosis in paediatric patients.

Necrosis of bone marrow is a very rare condition with a prevalence ranging from 0.15 to 7 percent. It is mostly not compatible with life. We diagnosed four cases of necrotic marrow out of 830 bone marrow aspirations done in last five years of time. All were paediatric patients having peripheral pancytopenia. Three out of four patients expired within one month of diagnosis.

Congenital spinal lipomas--tumor versus hamartoma.

Congenital spinal lipomas as a form of dysraphism are frequently reported in literature. A few studies have highlighted their histologic features and found them different from lipomas in other parts of the body. In a review of eight cases of spinal lipomas, we found heterotopic tissue in seven. Neural tissue, muscle, bone and cartilage were frequently encountered. The presence of meningothelial cells in one case was an unusual finding. These findings support the concept of their hamartomatous origin. Malignancy, occurring later in life in one of the heterotopic elements is known, though uncommon, and is one of the reasons, besides neurologic deficit, for long term follow-up.

Do all grade I lesions on colposcopy need to be biopsied?

The present study intends to correlate grade I atypical transformation zone (ATZ) on colposcopy with cytology & histology in 51 patients by retrospective data analysis. Indications of colposcopy were inflammatory smears with unhealthy cervix (37/51). Atypical squamous cells of unknown etiology (2/51) & squamous intraepithelial lesions on cytology (12/51). All the patients exhibited grade I lesions on colposcopy & underwent directed biopsy. On histology chronic cervicitis was the commonest finding 70.6% (36/51) & CIN was found in 19.6% (10/51), out of which CIN II-III occurred only in 3.92% (2/51). Overcall rate of colposcopy for grade I lesions was 80.39%. Age, parity, the postcoital or contact bleeding did not correlate with the histological positivity of the lesions. Grade I ATZ with inflammatory smears revealed CIN II-III only in 2.7% (1/37) while with low grade SIL cytology there was no moderate or severe dysplasia. However Grade I lesions in association with high grade SIL exhibited CIN II-III lesions in 16.6% (1/6). Therefore grade I lesions in presence of inflammatory or low grade SIL smears can be observed & biopsied only if the changes persist. However association of high grade SIL with grade I ATZ calls for immediate biopsy.

A study on physiological changes in certain psychosomatic disorders with reference to cortisol, blood glucose and lipid profile.

Plasma cortisol, blood glucose, serum lipids and lipoproteins were estimated in diseased human subjects and normal control volunteers. Serum triglyceride (Tg) total cholesterol (Tc) and cholesterol content of very low density lipoprotein (VLDLc), low density lipoprotein (LDLc) and high density lipoprotein (HDLc) were assayed under lipid profile. Clinical investigations were carried out on 115 subjects which involved 30 control, 25 irritable bowel syndrome (IBS), 30 bronchial asthma and 30 rheumatoid arthritis patients. The results of this preliminary study showed a significant change in the levels of all the biochemical parameters in diseased subjects in comparison with controls. Increased levels of atherogenic lipids, Tg, VLDLc and LDLc were found in rheumatoid arthritis subjects. This suggests that arthritis subjects are relatively at higher risk of developing coronary heart disease. Furthermore hypercholesterolemia may aggravate the risk condition in arthritis patients by artereosclerosis. The significant elevation in the levels of plasma cortisol reveals the fact that rheumatoid arthritis is a stabilized and chronic psychosomatic disorder, since, homeostatic competence is disrupted following decline in the tendency of stress-response to return to normalcy.