Hypothyroidism: A reversible aetiology of dilated cardiomyopathy.

Hypothyroidism has various cardiovascular manifestations, impairment of LV diastolic function being the commonest. We hereby report a young female who presented to us with features of congestive heart failure and on subsequent work-up she was diagnosed as a case of dilated cardiomyopathy of reversible aetiology, i.e., hypothyroidism.

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.

Severe primary antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is characterised by recurrent venous or arterial thrombosis and/or fetal losses. In APS, the homeostatic regulation of blood coagulation is altered, however, the mechanism of thrombosis is not yet defined and it has varied manifestations. Deep vein thrombosis with or without pulmonary embolism is the most common manifestation followed by arterial occlusion of cerebral, coronary and other arteries including subclavian, retinal, renal and pedal arteries. We report a case of a 42 years old female, with severe primary APS, who presented with symmetrical peripheral gangrene, an uncommon presentation and was treated successfully.

Testicular mixed germ cell tumor metastasizing to heart.

A 21 years old male presented with low grade fever, hemoptysis and progressively increasing dyspnoea of four month duration followed by acutely developing dizziness, hypotension, convulsion and altered sensorium. He had been operated (left inguinal orchidectomy) for left testicular swelling two years back with high alpha-fetoprotein and normal beta-human chorionic gonadotropin (beta-hCG). In view of this a possibility of metastasis secondary to a malignant testicular tumor was considered. Echocardiography demonstrated a large intracardiac mass, chest computed tomography (CT) revealed intracardiac mass, mediastinal masses and left sided pleural effusion. The histopathology revealed testicular mixed germ cell tumor (MGCT). This case is presented to demonstrate uncommon cardiac manifestations of secondary spread of testicular malignancy.

Iron deficiency anaemia in sickle cell disorders in India.

BACKGROUND & OBJECTIVE: Iron deficiency anaemia (IDA) is uncommon in individuals with sickle cell disease (SCD) because of availability of an adequate iron source potentially from increased red cell turnover and from blood transfusions. Also, iron deficiency anaemia can often go unnoticed because the sickle cell disease patients are already anaemic. Iron deficiency in sickle cell patients may result in lowering the intracellular haemoglobin concentration and this may ameliorate sickling. The present study was undertaken to determine the prevalence of iron deficiency anaemia and the response of iron supplementation in sickle cell disorders in tribal population of the four States viz. Maharashtra, Gujarat, Orissa and Tamil Nadu. METHODS: A total of 8434 individuals (7105 AA, 1267 AS and 62 SS) were tested for zinc protoporphyrin/haem (ZPP/H) ratio and haemoglobin levels. Twenty two sickle cell anaemia (SS), 47 sickle cell trait (AS) and 150 normal control (AA) individuals who were iron deficient, were given iron therapy for a period of 12 wk and the laboratory investigations were repeated at the 13th wk. RESULTS: Sixty seven per cent of subjects with sickle cell anaemia and 26 per cent with sickle cell trait had elevated ZPP/H ratios (>80 micromol/mol) as against 22.8 per cent of normal individuals. The elevated ZPP/H ratios is an indicator of microcytic anaemia of iron deficiency. Following iron therapy, an improvement in the Hb levels and ZPP/H ratios was observed in both sickle cell disorders and normal individual cases. INTERPRETATION & CONCLUSION: This study suggests that iron deficiency anaemia is an important problem in Indian sickle cell anaemia patients and iron supplementation should be given only in proven cases of iron deficiency anaemia.

Varied distribution of RhD epitopes in the Indian population.

BACKGROUND: Inhabited by more than 4000 caste and tribal groups, India has an extremely heterogenous population. For thousands of years many tribal groups have practised endogamy and are practically genetically isolated. Traditionally, polyclonal anti-D reagent has been used for RhD typing; though monoclonal antibodies are increasingly being used. As a result, blood banks find it difficult to assign the RhD status to an increasing number of people. As monoclonal anti-D typing reagents may not detect all RhD antigen epitopes, we studied the RhD antigen epitope heterogeneity in different population groups in India. METHODS: Red cells of 5315 RhD-positive individuals belonging to different castes and tribes of India were tested with 30 different epitope-specific monoclonal anti-D antibodies. RESULTS: No single monoclonal antibody could detect all RhD-positive red cells detected by polyclonal antisera. The highest proportion of D antigen was detected by LHM 76/55 and BRAD-8 (98%) monoclonal antibodies. CONCLUSION: We need to determine the correct mix of monoclonal antibodies that will detect nearly all RhD antigens detected by polyclonal anti-D sera. Similarly, before accepting monoclonal anti-D for therapeutic use, it would be necessary to determine the appropriate ones for use in the Indian population.

Elevated red cell volume in North Indian students.

In a survey for beta-thalassemia carrier status among students in the State of Punjab in India, a surprisingly large number were found to have an elevated red cell volume over 99 fl. The finding was predominantly but not exclusively in females. Similar student surveys from other states showed less macrocytosis. Follow-up tests in a group of affected students were carried out. Volunteers were asked to modify their diet then after six months they were provided with oral vitamin B12. The resulting changes are reported and the implications of the probable vitamin B12 and or folic acid deficiency are considered.

Production of murine monoclonal anti-B.

BACKGROUND & OBJECTIVE: Monoclonal antibodies against red blood cell antigens used in research and as diagnostics in India are commercially procured from western countries. Indigenously generated potent clones are not available in India. Hence, the objective of the present study was to raise potent murine monoclonal antibodies against A, B and H blood group antigens indigenously and establish a stable clone of anti-B secreting cells. METHODS: Spleen cells of female BALB/c mice immunized with B group red blood cells were fused in presence of polyethylene glycol (PEG) 1500 with a mouse myeloma cell line Sp 2/0 Ag. 14 in hypoxanthine aminopterine thymidine (HAT) selective medium and incubated at 37 degrees C, 5 per cent CO(2) and 95 per cent humidity for a week. RESULTS: The culture supernatant of the wells showing anti-B activity, were further subcloned and a clone 2C4D5F10 was generated which showed a good potency, avidity and specificity. INTERPRETATION & CONCLUSION: The anti-B clones thus produced indigenously provided a useful reagent in blood group typing. The unlimited availability unlike polyclonal antisera makes this reagent more cost-effective. It also ensures a regular supply with the similar specificity.

Flowcytometric evidence of platelet activation in patients on aspirin following myocardial infarction.

BACKGROUND: Following a myocardial infarction, patients are usually started on long term antiplatelet therapy with aspirin in a dose of 80-150 mg/day. However, there are no quick and easy methods to assess the efficacy of the antiplatelet activity of aspirin. METHODS: We studied 60 consecutive patients (men, < 40 years of age) 8-10 weeks after they had had acute myocardial infarction. These patients were receiving 100 mg aspirin daily orally with or without b-blockers. We measured P-selectin expression and fibrinogen binding by flowcytometry at least 3 times over a period of 2 years in all the patients. We also studied 100 age- and sex-matched controls. RESULTS: Of the 60 patients, 30 (50%) showed both increased P-selectin and fibrinogen binding by platelets, suggesting platelet activation. Fourteen other patients had increased fibrinogen binding but normal P-selectin expression. Sixteen patients and all the controls had normal results of both tests. CONCLUSION: Our data show evidence of platelet activation in at least 50% of patients receiving 100 mg of aspirin daily. Flowcytometry for P-selectin expression and fibrinogen binding to platelets can be used to monitor antiplatelet therapy with aspirin following acute myocardial infarction.

Hemoglobin sickle D Punjab-a case report.

Compound heterozygosity for bS/bD results in a severe hemolytic anemia and a clinical syndrome similar to that of sickle cell disease. Here, we report a case of HbSD Punjab disease. A 10 year old female child residing at Nagpur, Maharashtra presented with severe hemolytic anemia, hepatosplenomegaly and occasional pains in bones and abdomen. Initially, she was thought to be a case of sickle cell anemia, however, with the help of HPLC and molecular analysis it was confirmed as HbSD Punjab disease.

Detection of two rare β -thalassemia mutations [-90 (C → T) and CD 26 (C → T)] among Indians.

BACKGROUND : β -Thalassemia (β -thal) is present in practically every caste group in Indians. Molecular characterization of β -thal in these groups has revealed an extremely heterogeneous picture. AIM : To identify all the mutations and to detect the novel mutations using a versatile mutation detection technique. MATERIALS AND METHODS : Denaturing gradient gel electrophoresis (DGGE) has been established to scan the entire β -globin gene to localize the mutation followed by DNA sequencing for characterization. The DNA samples from two families referred to us either for prenatal diagnosis or for DNA studies were studied. RESULTS : Atypical DGGE patterns in fragments B & A indicating the presence of the mutation, have been detected in both the families. DNA sequencing revealed two rare patterns fragments with patterns in fragments β -thal mutations [CD 26 (C→T) and -90 (C→T)]. CONCLUSION : DGGE is a useful mutation detection technique to identify β -thal mutations among the heterogeneous Indian population.

Nucleolar organising region evaluation using new NOR FISH probe.

We have carried out chromosomal analysis in a couple with repeated spontaneous abortions (RSA). The chromosomal analysis of male revealed 15ps+ and the chromosome 15 appeared as submetacentric, C- group chromosome. First time we have attempted fluorescence in situ hybridization (FISH) using NOR probe (dJ1174 A5) and FISH analysis revealed NOR duplication on chromosome 15 which was also quantitated using Q-FISH software. The identical NOR duplication also detected in chromosome preparations from products of conception. However, NOR studies in large group of patients is necessary to understand the role of NORs in RSA.

Thrombophilia in coronary artery disease: a double jeopardy.

Thrombophilia can be defined as an increased risk of thrombosis. The central event to the pathogenesis of any thrombotic episode is the perturbation of haemostasis, the cause of which may be genetic or environmental. The clinical manifestations of the chronic development of coronary artery atheroma are angina and acute myocardial infarction. In recent years literature is emerging on the role of different factors of blood coagulation in arterial thrombosis. Different coagulation factors, natural anticoagulants, platelet antigens and other factors such as homocysteine, lipoprotein (a), have been studied as risk factors for coronary artery disease (CAD). The results of many of these studies are contradictory. In India, there is an alarming rise in the number of young patients with myocardial infarction (MI) and an interesting feature is that a large majority of these patients lack the conventional risk factors. There have been scattered studies on the thrombophilia status among Indians. The management of thrombophilia can be done by a regimen of different drugs which has been evaluated in different clinical trials. Since the cost of thrombophilia investigations is quite phenomenal for a developing country like India, the selection of these investigations assumes an utmost importance.