The impact of intravenous thrombolysis in acute ischemic stroke in National Medical College, Kolkata: initial experience

Background: Acute ischemic stroke is a potentially treatable condition, if left untreated, lead to mortality and morbidity. This study was conducted to study clinical profile of patients with acute ischemic stroke receiving intravenous thrombolysis (r-TPA-alteplase) and to measure the outcome of thrombolysis.Methods: Retrospective observational study of 54 patients who underwent thrombolysis for acute ischemic stroke at National Medical College, Kolkata over a period of one year.Results: There was statistically significant improvement in NIHSS (p value-0.000) after intravenous thrombolysis.Conclusions: IV thrombolysis is feasible for AIS in governmental hospital in India.

Van der Knaap disease

Van der Knaap disease is a rare form of leukodystrophy, phenotypically characterized by megalencephaly, early-onset ataxia, pyramidal features, cognitive impairment, with an autosomal recessive inheritence. MRI Brain shows T1 and FLAIR hypointense subcortical cysts in mostly temporal lobes and in fronto-parietal subcortical areas. Authors report a 20 yr. girl with typical features.

Ross syndrome: a case report

Ross syndrome is a rare partial dysautonomic syndrome of unknown aetiology, characterized by segmental hypo/ anhidrosis associated with Holmes-Adie syndrome (tonic pupil and hypo/areflexia). The hypohydrosis or anhydrosis is patchy initially, later it becomes segmental or diffuse. This is due to affection of postganglionic cholinergic parasympathetic and sympathetic fibers involvement. There are a very few cases (approximately 50) have been reported in the literature since its original description. Author report a 22 years old male with classical features of Ross syndrome.

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.

Effect of inherited red cell defects on growth of Plasmodium falciparum: An in vitro study

Background & objectives: High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been linked to the resistance provided by these alleles against parasitic infestations. Numerous studies undertaken to demonstrate this correlation have generated conflicting results. This study was undertaken to investigate the abilities of various polymorphic erythrocytes to support in vitro growth of Plasmodium falciparum parasites. Methods: In this study under in vitro condition the ability of P. falciparum parasites to grow was assessed in the erythrocytes obtained from a total of 40 patients with various haemoglobinopathies, such as ?-thalassaemia (?-Thal), sickle cell anaemia, erythroenzymopathy-like glucose-6-phosphate dehydrogenase deficiency and membranopathy-like hereditary spherocytosis. Results: Significantly reduced in vitro invasion and growth of parasites was seen in the cultures containing abnormal erythrocytes than in control cultures containing normal erythrocytes (P< 0.05). The mean per cent parasitaemia comparison was also carried out among the three polymorphic erythrocyte groups, i.e. ?-Thal, sickle cell anaemia and enzyme-membranopathies. Interpretation & conclusions: Erythroenzymopathies and membranopathies were found to provide a more hostile environment for parasites, as the least parasitaemia was observed in these erythrocytes. The present in vitro study showed that P. falciparum did not grow well and did not invade well in erythrocytes obtained from common inherited red cell disorders.

Individualization of antiretroviral therapy - Pharmacogenomic aspect.

Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy).

Diagnostic Approach to Primary Immunodeficiency Disorders.

Primary immunodeficiency disorders (PIDs) are a heterogeneous group of inherited disorders that affect different components of the immune system. There are more than 150 different disorders which have been described till date. Despite major advances in the molecular characterization of PIDs over the last 20 years, many patients remain undiagnosed or are diagnosed too late with severe consequences. Recognizing different clinical manifestations of PID is the first most important step. It should be followed by use of appropriate diagnostic tools from a vast number of investigations available. This review will focus on important presenting features of PID and laboratory approach for diagnosis of suspected cases of PID.

Clinical and Immunological Profile of Systemic Lupus Erythematosus.

Pediatric onset systemic lupus erythematosus (SLE) is not uncommon and female to male ratio varies. Pediatric SLE patients have more severe disease at onset, higher rates of organ involvement and more aggressive clinical course than adults. We compared the clinical and immunological parameters among pediatric SLE and adult SLE from Western India. Twenty five children and 60 adult patients fulfilling American College of Rheumatology SLE criteria were included. Anti-nuclear antibodies, anti-dsDNA and complement (C3, C4) levels were tested. Of 25 pediatric SLE patients studied, 24% showed CNS involvement vs. 8.3% in adults SLE (P=0.0499). Lupus nephritis was seen in 75% adult patients vs. 52% among children. Hepatosplenomegaly was noted more among adult SLE 26.8% vs 12% among children. Alopecia was an exclusive features among adult SLE.

Electrolyte Imbalance in Cataract Patients.

100 cataract patients of IGGMC attending Biochemistry OPD for routine Blood sugar, were estimated for serum electrolyte level i.e. Sodium, Potassium level and compared with normal healthy age related ( 50-70 yrs) control by t test. Plasma Glucose level (to rule out Diabetes) and serum Creatinine (to rule out renal disorder) in both cases and control were also studied. Result of our study shows Elevation in serum Na level in cataract pts mean 148.52 + /-4.13 meq/lt compared to control mean 139.26 +/-3.08 meq/lt (p value 0.001) which is significantly high. Normal Serum Na level is required to maintain proper water electrolyte balance across lens membrane that in turn is also responsible for maintaining lens membrane permeability. Elevation in serum Na level in cataract pts may result into its further increase in aqueous humor of lens which may lead to osmotic imbalance across lens membrane and aggravate, progression of disease. We conclude that salt restricted Diet must be advised in Cataract patients so as to maintain normal electrolyte balance which may prevent further progression of disease.

HIV and malaria co-infection in Mumbai, western India.

Background & objectives: Conflicting reports exist regarding the HIV-1 infection on the risk of malaria. A transient almost one-log elevation in HIV viral load occurs during febrile malaria episodes. We prospectively studied malaria patients for HIV infection from Mumbai. Methods: A total of 171 malaria patients and 28,749 normal voluntary blood donors were studied for their HIV status. Diagnosis of malaria was done by microscopical examination of blood. HIV screening was done by detection of HIV-1 & 2 antibodies by micro well ELISA using Enzaids & J Mitra kits followed by confirmation using western blot (Innogenetics, Belgium) analysis. Results: Out of 171 malaria patients 13 (7.6%; Odds ratio= 4.45; p <0.0001) and 521 blood bank donors were found to be HIV reactive. Among 13 HIV reactive patients, eight patients were Elisa borderline reactive and western blot positive (p24), which may be due to cross-reactive antibodies. Five of 13 malaria patients found to be HIV-1 positive by ELISA and by western blot confirming HIV and malaria co-infection. Conclusion: Our findings suggest that HIV-1 and malaria co-infection can’t be ruled out in malaria endemic countries like India.

Human immunodeficiency virus therapeutics and pharmacogenomics.

Pharmacogenomics and pharmacogenetics are promising in development of a personalized treatment approach They are of paramount importance for basic immunology, for peptide based vaccine design (vaccinomics) drug monitoring in clinical setting and molecular pathophysiology of multifactorial diseases like cancer, tuberculosis, cardiac disorders, diabetes, asthma, HIV, etc

Incidence of malignancy and clonal chromosomal abnormalities in Fanconi anemia.

Background: Fanconi anemia (FA) is an autosomal recessive, cancer susceptibility disorder characterized by diverse clinical features, such as short stature, skeletal or skin abnormalities, progressive bone marrow (BM) failure, and increased risk of malignancies. Clonal chromosomal abnormalities are frequently reported in FA patients transformed to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aim: To study the incidence of malignancy and clonal chromosomal abnormalities in FA patients. Materials and Methods: Thirty-eight clinically diagnosed FA patients were studied at the time of diagnosis and the patients were followed-up for a maximum of 28 months at 3-month intervals. The median duration of follow-up of these patients was 19.8 months. Chromosomal breakage investigation using mitomycin C (MMC)- and diepoxybutane (DEB)-induced peripheral blood cultures were stimulated with phytohemagglutinin. Cytogenetic study was done on the BM cells to detect clonal chromosomal aberrations. Results: Eleven (28.95%) out of 38 patients developed malignancies, including 6 (54.54%) MDS, 4 (36.36%) AML, and 1 (2.63%) squamous cell carcinoma. The clonal chromosomal abnormalities were detected in 5 (45.45%) FA patients who developed malignancies and the type of chromosomal abnormality detected were monosomies 5, 7, trisomy 10, dup(1)(q12-q24), and inv(7)(p11pter). Conclusion: The FA patients have a high risk of developing malignancies, and clonal chromosomal abnormalities play an important role in the prognosis of the disease. Therefore, FA patients need to be followed-up at regular intervals for early diagnosis and optimal management of the disease.

Iron Deficiency as a Risk Factor for First Febrile Seizure.

We conducted this study to determine the role of iron deficiency as a risk factor for first febrile seizure in children. Fifty children between 6 months to 6 years with first febrile seizure (Cases) and 50 children with febrile illness but without convulsions (Controls) were enrolled from the pediatric ward of a tertiary care hospital. Iron deficiency was determined by estimation of hemoglobin, red blood cell indices and serum ferritin. The mean serum ferritin level (μg/L) was significantly low in Cases (31.9 ± 31.0) as compared to Controls (53.9 ± 56.5) with P = 0.003. Iron deficiency could be a potential risk factor for febrile seizure in children.

Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and nonfamilial vitiligo.

Background: Various studies worldwide suggest that human leukocyte antigen (HLA) region may be involved in the genetic susceptibility of vitiligo but little information is available from India. Aim: To find the HLA associated susceptibility to develop vitiligo in Indian patients and to detect role of HLA in familial vitiligo. Methods: This was a case controlled study which included all patients suffering from vitiligo over a period of one and half years. Clinical details were noted and sera collected from these patients were screened for the presence of HLA class I antibodies. The clinical features and HLA antigens were assessed and comparison was made between patients with familial and nonfamilial vitiligo. Results: Out of 114 patients studied, 84 had family history and 30 had no family history. Patients with family history of vitiligo have higher chances of acquiring vitiligo if first degree relatives are affected compared to if second degree relatives are affected. Family history of vitiligo is associated with an early onset of vitiligo (<20 years). There was no statistically significant difference in the type, stability, and severity of vitiligo in both the groups. HLA results in both the groups revealed increase in HLA A2, A11, A31, A33, B17, B35, B40, and B44 alleles while HLA A9, B13, and B53 alleles were decreased. Family history was associated with HLA A2, A28, A31, and B44 alleles. Early onset of vitiligo (<20 years) was significantly associated with HLA A2, A11, B17, B35, and B44 alleles. The patients with severe affection (>10% area) showed in significant association with HLA A10 and B8. Conclusion: Family history of vitiligo is associated with an early onset of vitiligo. There is no correlation of family history with the type of vitiligo, stability of lesions, and areas involved. Severity is not associated with family history. Apart from other alleles, alleles A2, and B44 play a significant role in vitiligo in the Indian patients.

Microsatellite diversity among the primitive tribes of India.

The present study was undertaken to determine the extent of diversity at 12 microsatellite short tandem repeat (STR) loci in seven primitive tribal populations of India with diverse linguistic and geographic backgrounds. DNA samples of 160 unrelated individuals were analyzed for 12 STR loci by multiplex polymerase chain reaction (PCR). Gene diversity analysis suggested that the average heterozygosity was uniformly high ( >0.7) in these groups and varied from 0.705 to 0.794. The Hardy-Weinberg equilibrium analysis revealed that these populations were in genetic equilibrium at almost all the loci. The overall GST value was high (GST = 0.051; range between 0.026 and 0.098 among the loci), reflecting the degree of differentiation/heterogeneity of seven populations studied for these loci. The cluster analysis and multidimensional scaling of genetic distances reveal two broad clusters of populations, besides Moolu Kurumba maintaining their distinct genetic identity vis-à-vis other populations. The genetic affinity for the three tribes of the Indo-European family could be explained based on geography and Language but not for the four Dravidian tribes as reflected by the NJT and MDS plots. For the overall data, the insignificant MANTEL correlations between genetic, linguistic and geographic distances suggest that the genetic variation among these tribes is not patterned along geographic and/or linguistic lines.