Melt-compounded composites of ethylene vinyl acetate with magnesium sulfate as flexible EPR dosimeters: Mechanical properties, manufacturing process feasibility and dosimetric characteristics.

Novel polymeric composites for radiation dosimetry were developed. The composites were prepared by solvent-free melt compounding of ethylene vinyl acetate (EVA) (40% vinyl) and magnesium sulfate (MgSO4). Mechanical properties, melt flow characteristics and dosimetric properties were investigated. The composites with up to 50% (wt) of MgSO4 were flexible and capable of flow. The dose response of the EPR signal of the composites was studied in the dose range 3Gy-4kGy and found to be linear between 18Gy and 4kGy. The reproducibility of dose measurements was good. The signal fading rate and the energy dependence of the dose response were found to be acceptable.

Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and perforin-mediated CD4(+) T-cell lysis.

Immune-driven adaptation of hepatitis B virus genotype D involves preferential alteration in B-cell epitopes and replicative attenuation--an insight from human immunodeficiency virus/hepatitis B virus coinfection.

An important driving force behind the sequence diversity of hepatitis B virus (HBV) is viral adaptation to host immune responses. To gain an insight into the impact of host immunity on genetic diversification and properties of HBV, we characterized HBV of genotype D from treatment-naive hepatitis B e antigen-positive (EP) and hepatitis B e antigen-negative (EN) patients with chronic hepatitis B (CHB), where HBV is under stronger immune pressure, with that of HBV derived from human immunodeficiency virus (HIV)/HBV-coinfected individuals, where HIV infection has significantly weakened the immune system. Full-length sequence analysis showed that HBV heterogeneity was most extensive in EN-CHB followed by EP-CHB and HIV/HBV coinfection. The relative magnitude of non-synonymous changes within B-cell epitopes was greater than that in T-cell epitopes of HBV open reading frames (ORFs) in both EP-CHB and EN-CHB. Nine amino acid substitutions were identified in B-cell epitopes and one in a T-cell epitope of HBV in EN-CHB, most of which resulted in altered hydrophobicities, as determined using the Kyte and Doolittle method, relative to wild-type residues found in HBV from the HIV-positive group. Additionally, 19 substitutions occurred at significantly higher frequencies in non-epitope regions of HBV ORF-P in EN-CHB than HIV/HBV-coinfected patients. In vitro replication assay demonstrated that the substitutions, particularly in reverse transcriptase and RNaseH domains of ORF-P, resulted in a decline in replication capacity of HBV. Hence, our results indicate that HBV adapts to increasing immune pressure through preferential mutations in B-cell epitopes and by replicative attenuation. The viral epitopes linked to immune response identified in this study bear important implications for future HBV vaccine studies.

Synthesis of a flexible poly(chloroprene)/methyl red film dosimeter using an environment-benign shear compounding method.

The paper reports synthesis of a new film dosimeter based on a solvent-free route. Methyl red (MR) dye was introduced into poly(chloroprene) (PC) in various concentrations. The films were intensely red with λmax ~515nm. The absorbance decreased linearly with absorbed radiation dose up to 30kGy without a significant change in λmax. Color coordinates of the films were also analyzed. Optical micrographs of the films showed no signs of inhomogeneous distribution of MR in the PC matrix, which was attributed to the polarity of PC. Radiation sensitivity, dose response linearity, effects of irradiation temperature and humidity, as well as the rate of fading, were also investigated.

Benefits and limitations of fine needle aspiration cytology in the diagnosis and classification of leprosy in primary and secondary healthcare settings.

OBJECTIVES: The goal of the World Health Organization (WHO) is to eliminate leprosy as a public health problem. This will only be possible when all patients are detected and cured using multidrug therapy, which requires accurate diagnosis prior to treatment. The objective of this study was to evaluate the possibility of the diagnosis of leprosy lesions by fine needle aspiration cytology according to a modification of the Ridley-Jopling scale, as it can be used in primary and secondary healthcare centres, especially in low-resource settings in which leprosy is prevalent. METHODS: A prospective study comprising 54 cases with cardinal features of leprosy was performed. Among the 54 cases, 27 patients consented to a histopathological biopsy procedure. The slides were stained with Giemsa, modified Ziehl-Neelsen, Papanicolaou and haematoxylin and eosin methods. RESULTS: Among the 54 cases, 34 were reported as tuberculoid leprosy, five as mid-borderline (BB), three as borderline lepromatous (BL) and eight as lepromatous leprosy (LL); four were unsatisfactory. Histopathological study was performed in 27 cases, which showed cyto-histological correlation in 21 cases (78%). Agreement between histological and cytological diagnosis was achieved in 12 of the 15 tuberculoid cases, one of the three BB cases, one of the two BL cases and all seven LL cases. CONCLUSION: With the implementation of the WHO classification based on patch counting, there is the possibility of the over-treatment of paucibacillary cases and under-treatment of multibacillary cases. Cytology in terms of cellular type morphology and bacteriological study can complement the WHO classification.

New HBV subgenotype D9, a novel D/C recombinant, identified in patients with chronic HBeAg-negative infection in Eastern India.

Genome diversity is a hallmark of hepatitis B virus (HBV), which allowed its classification into 10 genotypes (A-J) and numerous subgenotypes. Among them, Genotype D is currently segregated into eight subgenotypes (D1-D8). Here, we report the identification and characterization of a novel subgenotype within genotype D of HBV from chronic hepatitis B e antigen (HBeAg)-negative patients of Eastern India. Phylogenetic tree analysis based on complete genome sequences revealed that six of 39 HBV/D isolates formed a distinct cluster supported by high bootstrap value and had nucleotide divergence >4% relative to the known D subgenotypes (D1-D8), justifying their assignment into a new subgenotype (D9). By comparing the amino acid sequences of the four ORFs of HBV/D9 with D1-D8, 36 specific residues, including a unique one (E(112) in the core region), were identified that could be considered as a signature of D9. Further analysis by Simplot, BootScan and jpHMM demonstrated that D9 resulted from a discrete recombination with genotype C over the precore-core region. This type of recombination has not been described previously as all C/D recombinants reported so far possessed genotype C backbones with mosaic fragments derived from HBV/D. Interestingly, compared to other subgenotypes of HBV/D, D9 isolates had a higher frequency of mutations (A1762T and G1764A) in the basal core promoter region that had been implicated in the development of hepatocellular carcinoma. Further investigations are needed to determine the overall prevalence and clinical significance of these newly characterized D9 strains and to assess the impact of inter-genotypic recombination on viral properties.

Tracking the naturally occurring mutations across the full-length genome of hepatitis B virus of genotype D in different phases of chronic e-antigen-negative infection.

Hepatitis B e-antigen (HBeAg)-negative chronic HBV infection is highly prevalent in several parts of the world, including India, with the clinical spectrum ranging from inactive carrier (IC) state to chronic 'e-negative' hepatitis B (CHB) and culminating in advanced liver disease such as cirrhosis (LC). The present study has for the first time investigated the natural diversity of HBV belonging to genotype D in treatment-naïve Indian patients representing the above phases of HBeAg-negative infection to identify candidate mutations associated with each disease state. Studies of full-length HBV/D sequences revealed that the progressive accumulation and persistence of mutations in basal core promoter, negative regulatory element, Pre-core region, the B- and T-cell epitopes of X protein as well as deletions in the PreS region contribute significantly to disease progression from IC through CHB to LC. In addition, the development of CHB was associated with a significant increase in viral variants characterized by mutations in enhancer II, preS1 promoter, T-cell epitope of core and B-cell epitope region of PreS1. While few of the mutations were previously reported in the context of HBV genotypes B and C, others had not been documented before. Our results thus highlight a distinct pattern of mutation in HBV/D that may help in predicting clinical outcomes of HBeAg-negative infection and have implications for better clinical management of the patients.

Disseminated lipogranulomatosis.

Farber disease or disseminated lipogranulomatosis is a rare inherited disorder of lipid metabolism resulting from a defect in ceramide degradation. Because of the feature of nodular swellings around various joints, this may sometimes be confused with juvenile idiopathic arthritis. We report a 4-year-old boy with Farber disease who presented with nodular swellings around the joint, angle of the mouth and conjunctiva, and was subsequently diagnosed to be a case of Farber Disease.

Ghosal type hemato-diaphyseal dysplasia: a rare variety of Engelmann's disease.

Ghosal type hemato-diaphyseal dysplasia is a recently described clinical entity. The authors describe such a case with severe anemia requiring transfusions and with clinical and radiological evidence of diaphyseal dysplasia. Very few such cases are reported in world literature.

Jervell-Lange Nielsen syndrome in a family with the long QT Syndrome (LQTS).

A child with Jervell-Lange Nielsen syndrome is presented from Kolkata. Family study showed that the other family members are suffering from long QT syndrome. The child had frequent syncopal attack and very prolonged QT interval requiring left cardiac sympathetic denervation and beta-blocker therapy as patient could not afford implantable defibrillator and cardiac pacing.

Human papillomavirus prevalence in postradiotherapy uterine cervical carcinoma patients: correlation with recurrence of the disease.

To understand the role of human papillomavirus (HPV) in recurrence of uterine cervical cancer (CA-CX) after radiotherapy, we have analyzed the HPV prevalence in the exfoliated cells of 56 patients and their corresponding plasma. HPV DNA was detected in exfoliated cells of 78% (44/56) patients (HPV-16, 68%; HPV-18, 14%; HPV-X [other than 16, 18], 11%; and mixed infection of HPV-16 and HPV-18 in three cases). HPV DNA in plasma was present in only 25% (11/44) of the HPV-positive exfoliated cells (positive predictive value, 100%; negative predictive value, 27%) with concordance in HPV types. The recurrence of the disease was significantly associated with the presence of HPV in the exfoliated cell (P= 0.01) and plasma (P= 0.007) as well as high viral load in the exfoliated cell (P= 0.0002). Kaplan-Meier disease-free estimates have also shown the significant association between HPV prevalence in plasma and recurrence of the disease (P= 0.045). Thus, it indicates that in postradiotherapy CA-CX patients, the high viral load in the exfoliated cell as well as HPV presence in the plasma samples could be used in early detection of the patients at increased risk for disease recurrence and progression.

Hemiconvulsion, hemiplegia, epilepsy syndrome and inherited protein S deficiency.

A nine-year-old Nepalese girl developed hemiconvulsion, hemiplegia, epilepsy syndrome (HHE syndrome) after an episode of right-sided focal status epilepticus following acute gastroenteritis. She had left middle cerebral artery (MCA) territory infracts due to inherited protein S deficiency.

Uncomplicated falciparum malaria complicated by salmonella septicaemia: cause not coincidence.

A male patient of 10-year-old presented with fever, headache and vomiting for last few days. He was being treated with antimalarial drugs. On 14th day of illness he again showed rise of temperature. His blood culture showed growth of Salmonella typhi. He was treated with ceftriaxone and responded favourably. Here uncomplicated falciparum malaria developed a secondary infection with salmonella during hospital stay. This uncommon association was noted rather than a mere coincidence, which rarely reported in literature.

Epidemiological aspects of acute childhood poisoning among patients attending a hospital at Kolkata.

A retrospective study from a tertiary care teaching hospital in Kolkata revealed 3.6% of total paediatric admissions were due to poisoning. Majority of the cases included oral/chemical poisoning followed by biological/envennomation. Kerosene was the commonest among all poisoning. Most of the cases were accidental.

Virchows node: rare presentation of childhood hepatocellular carcinoma.

Cervical (supra-clavicular) lymphadenopathy may not always be due to tuberculosis in children. Hepatocellular carcinoma in children even may present as supra clavicular lymphadenopathy (Virchow's node).

Prominence of symptoms and level of stigma among depressed patients in Calcutta.

A pilot study of 29 patients for research on clinical depression employed the framework of cultural epidemiology to examine illness-related experience, meaning, behaviour with a Bengali version of the explanatory Model Interview Catalogue (EMIC). This report examined patterns of distress and stigma with reference to the most troubling patient-specified symptom. All subjects were psychiatric outpatients in the Institute of Psychiatry, Calcutta, and met Diagnostic and Statistical Manual (DSM)-IV criteria for a major depressive episode. Only 5 patients (17.2%) identified sadness as the most troubling problem, and 48.3% specified pains and other somatic symptoms instead. An internally consistent stigma scale with Cronbach's alpha of .67, comprised 13 items, was used to assess stigma. In addition to the scale score for each subject, the contribution of each item was reported and compared. A suggestive, though not significantly lower value of the stigma score for patients reporting somatic symptoms as most troubling, compared with sadness, was consistent with findings from prior studies showing a positive relationship between the magnitude of depression and stigma. These findings are discussed with reference to their impact on recognition and help seeking among patients, and recognition and management of depression by general practitioner. Culturally distinctive presentations and social contexts of depression and other mental illnesses should be addressed in professional training and public health communications.