First living‐related liver transplant to cure factor VII deficiency

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first‐ever youngest baby reported worldwide. A six‐month‐old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life‐threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre‐, intra‐ and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency.     

Establishment of a Maternal Newborn Health Registry in the Belgaum District of Karnataka,India

Background

Pregnancy-related vital registration is important to inform policy to reduce maternal, fetal and newborn mortality, yet few systems for capturing accurate data are available in low-middle income countries where the majority of the mortality occurs. Furthermore, methods to effectively implement high-quality registration systems have not been described. The goal of creating the registry described in this paper was to inform public health policy makers about pregnancy outcomes in our district so that appropriate interventions to improve these outcomes could be undertaken and to position the district to be a leader in pregnancy-related public health research.

Methods

We created a prospective maternal and newborn health registry in Belgaum, Karnataka State, India. To initiate this registry, we worked with the Ministry of Health to first establish estimated birth rates and define the catchment areas of the clusters, working within the existing health system and primary health centers. We also undertook household surveys to identify women likely to become pregnant. We then implemented monitoring measures to ensure high quality and completeness of the maternal newborn health registry. All pregnant women in the catchment area were identified, consented and enrolled during pregnancy, with follow-up visits to ascertain pregnancy outcomes and mother/infant status at 42-days postpartum.

Results

From 2008 through 2014, we demonstrated continued improvements in both the coverage for enrollment and accuracy of reporting pregnancy outcomes within the defined catchment area in Belgaum, India. Nearly 100% of women enrolled had follow-up at birth and 99% had 42-day follow-up. Furthermore, we facilitated earlier enrollment of women during pregnancy while achieving more timely follow-up and decreased time of reporting from the date of the pregnancy event.

Conclusions

We created a pregnancy-related registry which includes demographic data, risk factors, and outcomes allowing for high rates of ascertainment and follow-up while working within the existing health system. Understanding the elements of the system used to create the registry is important to improve the quality of the results. Tracking of pregnancies and their outcomes is an important step toward reducing maternal and perinatal mortality.

     

The Contribution of Anxiety Sensitivity to Obsessive–Compulsive and Anxiety Symptoms in a Naturalistic Treatment Setting

Anxiety sensitivity (AS), a fear of arousal-related sensations, is prevalent in a number of disorders. We examined the relationship between internalizing symptoms and the anxiety sensitivity components of physical, social, and cognitive concerns in a sample of 165 patients seeking treatment in a clinic specializing in cognitive behavioral therapy for anxiety-related disorders. Social anxiety symptoms were associated with greater social concerns. Cognitive concerns were characteristic of both depression and generalized anxiety symptoms, suggesting these two classes of symptoms may share AS symptomatology. Physical concerns were specifically related to panic symptoms. Although obsessive–compulsive symptoms were related to cognitive concerns using univariate regression, these symptoms were not strongly related to any of the anxiety sensitivity components when the correlation between disorders was taken into account. Thus, within the internalizing symptoms studied here, the anxiety sensitivity domains were most relevant to panic, social anxiety, generalized anxiety, and depressive symptoms and less related to obsessive–compulsive symptoms.     

An immunochromatographic dipstick as an alternate for monitoring of heroin metabolites in urine samples

Heroin use and addiction pose serious risks and side effects due to overdose. Quantification of heroin in biological samples is challenging due to rapid deacetylation of heroin to its active metabolites. In this study, we report the quantification of metabolic degradation of heroin by-products in biological urine samples. The presence of the drug was monitored after oral administration of heroin at different time intervals. Various biophysical techniques, such as high performance liquid chromatography (HPLC) and mass spectrometry (MS) were used to evaluate the presence of the drug. A competitive fluorescence based immunoassay was developed with a limit of detection (LOD) up to 0.01 ng mL⁻¹ and the IC₅₀ value was 0.1 ng mL⁻¹, while the dipstick assay shows a LOD up to 5 ng mL⁻¹. Rapid detection of narcotic drugs was carried out for biological urine samples collected at various time points. Validation of the developed dipstick was carried out for the standard as well as the spiked urine samples by fluorescence based immunoassay (FIA), using anti-morphine antibodies. A strong correlation (R = 0.94) was obtained between the developed dipstick and FIA assay for biological urine samples collected at various time points. The developed immunochromatographic dipstick is highly sensitive, field applicable and cost effective, and can serve as a first choice for the monitoring of narcotic drugs in blood, urine and saliva in drug addicts and athletes.

Pathway of heroin degradation post oral administration in mice.     

Synthesis of non-toxic,biocompatible, and colloidal stable silver nanoparticle using egg-white protein as capping and reducing agents for sustainable antibacterial application

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity. However, their poor long-term stability in different environments, namely, pH, ionic strength, and temperature, and cytotoxicity toward mammalian cells has restricted their more extensive applications. Hence, there is urgent need to develop highly biocompatible, non-toxic, and stable silver nanoparticles for wide-ranging environments and applications. In the present study, a simple, sustainable, cost-effective and green method has been developed to prepare highly stable aqueous colloidal silver nanoparticles (AgNPs-EW) using the ovalbumin, ovotransferrin, and ovomucoid of egg-white as reducing and capping agents accomplished under the irradiation of direct sunlight. Then, we evaluated the effects of freezing–drying (lyophilization) and freeze–thaw cycles on the stability of AgNPs-EW in aqueous solution under visual inspection, transmission electron microscopy, and absorbance spectroscopy. In addition, we studied the antibacterial activity against Salmonella typhimurium and Escherichia coli, carried out biocompatibility studies on chicken blood, and tested acute, chronic toxicity in Drosophila melanogaster. The results suggest that AgNPs-EW did not aggregate upon freeze-thawing and lyophilization, thus exhibiting remarkable stability. The antibacterial activity results showed that the AgNPs-EW had the highest antibacterial activity, and the minimum inhibitory concentration (MIC) of AgNPs-EW for E. Coli and S. typhimurium were 4 and 6 μg ml⁻¹, respectively. The biocompatibility study revealed that the AgNPs-EW did not induce any hemolytic effect or structural damage to the cell membranes of chicken erythrocytes up to a concentration of 12 μg ml⁻¹. Similarly, no acute and chronic toxicity was observed on melanization, fecundity, hatchability, viability, and the duration of development in the 1^st generation of Drosophila melanogaster at the concentration range of 10 mg L⁻¹ to 100 mg L⁻¹ of AgNPs-EW, and all the flies completed their full developmental cycle. Therefore, the present study successfully demonstrated the green and sustainable preparation of non-toxic AgNPs-EW having good biocompatibility, enhanced colloidal stability, and antibacterial activity. Hence, the synthesized AgNPs-EW could be used for the development of an antimicrobial formulation for controlling microbial infection.

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity.     

Evidence for activation of cellular immune responses in patients with acute hepatitis E.

INTRODUCTION: Although acute hepatitis E virus (HEV) infection is known to induce IgM and IgG humoral host immune responses, little is known about occurrence of cellular responses in this infection. We looked for evidence of lymphocyte sensitization to HEV peptides in patients with acute HEV infection. METHODS: peripheral blood lymphocytes were obtained from patients with acute hepatitis E and healthy controls. Proliferation of these lymphocytes in the presence of each of seven peptides with amino acid sequences corresponding to open reading frames 2 and 3 proteins of HEV (3 and 4 peptides, respectively) were studied; no peptide was added to control wells. Proliferative responses with stimulation indices exceeding 3.0 were taken as positive. RESULTS: More patients showed reactivity to two or more HEV peptides than did controls (11/21 vs 5/22, p<0.05). Reactivity to one peptide corresponding to open reading frame 2 of HEV was more frequent in patients than in controls (7/21 vs 1/22, p<0.05). CONCLUSION: Our results show that lymphocytes of patients with acute hepatitis E show sensitization to HEV peptides. This may have significance in understanding the pathogenetic mechanisms of liver injury in this infection.     

Clinical, haematological and histomorphological profile of adult myelodysplastic syndrome. Study of 96 cases in a single institute

Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders characterised by ineffective and dyspoietic haematopoiesis. The natural history of these disorders is variable and ranges from a chronic to a rapid course towards leukaemic progression. Certain shortcomings have been encountered in the French-American-British (FAB) classification over the years, and therefore there is a need for an alternative method of classification. In 1999, the WHO published a revised classification of MDS. In the present study, we have analysed the clinical, haematological and histomorphological features in 96 cases of primary MDS seen in the department of haematology at the All India Institute of Medical Sciences (AIIMS) over a 6-yr period (1996-2001). Both FAB and WHO classifications have been incorporated and the Bournemouth scoring system applied in each case at presentation. The Bournemouth scoring system, in the absence of a cytogenetic study, offers a good prognostication and long-term survival estimate.     

Aortoarteritis presenting with hypoparathyroidism

Clinical manifestations of aortoarteritis (Takayasu's arteritis) are varied, depending on the involved segment of the aorta and its branches. A case of a young Indian woman with aortoarteritis presenting primarily with hypoparathyroidism is reported. Aortogram showed total occlusion of the arch arteries. To the best of our knowledge, the occurrence of hypoparathyroidism in aortoarteritis has not been reported. Possible mechanisms of such an involvement are discussed.