Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects : evidence for increased production of endothelin in pulmonary circulation

We have characterized the mutations in 1050 carriers of the β-thalassemia gene and analyzed their regional distribution in India. The majority of β-thalassemia carriers were migrants from Pakistan and their pattern of mutations differed from the rest. The frequency of the 619-bp deletion was 33.3% among the migrants from Pakistan, 8–17% in the northern states, and less than 5% in the other states. Among non-migrant subjects, the predominant mutation was IVS-I-5 (G→C), varying from 85% in the southern states and 66–70% in the eastern states to 47–60% in the northern states. The mutation IVS-I-1 (G→T) was observed at high frequency among the migrants from Pakistan (26.2%), but with very low/ zero frequency in the other states. Mutations at codons 8/9 (+G) and codons 41/42 (–CTTT) were distributed in all regions of India with a frequency varying from 3% to 15%. Only eight of 12 published rare mutations were observed in subjects from different parts of India. Mutations of codon 5 (–CT) and codons 47/48 (+ATCT) were found exclusively in migrants from Pakistan, and mutation –88 (C→T) was detected only in subjects from Punjab, Haryana, and Uttar Pradesh. Using the amplification refractory mutation system technique, mutations were successfully identified in 98.2% of subjects. Overall, 91.8% of the subjects had one of the five commonest mutations [IVS-I-5 (G→C), 34.1%; 619-bp deletion, 21.0%; IVS-I-1 (G→T) 15.8%; codons 8/9 (+G), 12.1%, and codons 41/42 (–CTTT), 8.7%], 5.9% of the subjects had a less common mutation, while 1.8% of the carriers remained uncharacterized. The application of this knowledge has helped to successfully establish a program of genetic counselling and prenatal diagnosis of β-thalassemia in order to reduce the burden of this disease in India.

Regional distribution of β-thalassemia mutations in India

Anemia in children is commonly encountered by the family physician. Multiple causes exist, but with a thorough history, a physical examination and limited laboratory evaluation a specific diagnosis can usually be established. The use of the mean corpuscular volume to classify the anemia as microcytic, normocytic or macrocytic is a standard diagnostic approach. The most common form of microcytic anemia is iron deficiency caused by reduced dietary intake. It is easily treatable with supplemental iron and early intervention may prevent later loss of cognitive function. Less common causes of microcytosis are thalassemia and lead poisoning. Normocytic anemia has many causes, making the diagnosis more difficult. The reticulocyte count will help narrow the differential diagnosis; however, additional testing may be necessary to rule out hemolysis, hemoglobinopathies, membrane defects and enzymopathies. Macrocytic anemia may be caused by a deficiency of folic acid and/or vitamin B12, hypothyroidism and liver disease. This form of anemia is uncommon in children.

http://www.klinikaikozpont.u-szeged.hu/pedia/images/pdf/CME_AN/4ANFT/21.pdf

Anemia in children.

A service for prenatal diagnosis of beta-thalassaemia was introduced in Pakistan in May 1994. Two renowned Islamic scholars, consulted before the service was introduced, ruled that a pregnancy can be terminated if the fetus is affected by a serious genetic disorder, and if termination is before 120 days (17 weeks) of gestation. During the first 3(1/2) years of the service 300 couples requested the test. Almost all the couples had been informed by their treating doctors. Most diagnoses were made between 10 and 16 weeks of gestation, and only 15 (5%) were reached after the 16th week. DNA analysis was by the amplification refractory mutation system (ARMS). A multiplex ARMS was developed in which three primer combinations identified the mutations in 91.5% of the couples. In 13 couples (4. 3%) linkage analysis was required for the fetal diagnosis. In 47/53 (88.7%) women carrying an affected fetus the pregnancy was terminated. In six cases it was declined principally on religious grounds. Postnatal confirmation of the prenatal diagnosis was possible in 117 unaffected children. One year after the start of the service, interviews with 141 couples with an affected child showed that 72% knew of the availability of prenatal diagnosis. Thirty-two of the informed couples had had a pregnancy, but only 18 (56%) used prenatal diagnosis. The main reasons for non-utilization of prenatal diagnosis were the cost of the test and fear of undergoing the test, though some gave no clear explanation. This study demonstrates that prenatal diagnosis is feasible and acceptable in a Muslim country such as Pakistan.

Prenatal diagnosis of beta-thalassaemia in Pakistan: experience in a Muslim country.

Prevention of Thalassaemias and Other Haemoglobin Disorders

Prevention of thalassemia: a necessity in India.

We present our experience with the amplification refractory mutation system (ARMS) for the prenatal diagnosis of beta-thalassaemia in 415 pregnancies of 360 women. Five mutations of the beta-thalassaemia gene common in Asian Indians accounted for 89.2 per cent and rare mutations for 7.2 per cent of all mutant chromosomes, while 3.3 per cent of chromosomes remained uncharacterized. Identical mutations were present in both parents in 43.2 per cent of cases, due to caste-based marriages in India. A confirmed diagnosis was given in 401 (98.3 per cent) cases, of which a complete diagnosis (whether the fetus was normal, a carrier, or homozygous) was possible in 391 (94.2 per cent) of the cases. In 15 couples, the mutation was identified in only one parent. In nine of these, the identified mutation was not present in the fetus, predicting normal/carrier status, while in five the identified mutation was present in the fetus, suggesting carrier/affected status. The abortion rate was 3.9 per cent. Pitfalls in diagnosis were failure of oligonucleotides to work, maternal contamination, and false paternity. The ARMS provides an inexpensive, robust and non-isotopic method for the prenatal diagnosis of beta-thalassaemia in India. Recommendations are outlined for establishing a prenatal diagnostic service in developing countries.

Prenatal diagnosis of β‐thalassaemia: experience in a developing country

Carbon management is a strategic priority and organizations need to forecast carbon for that. We aim to find out the best ARIMA-GARCH model for forecasting conditional return and volatility of European Union Allowance (EUA) for all three phases of European Union Emissions Trading Scheme and the Rolled Over series. We use European Climate Exchange Dec 2007, Dec 2012, Dec 2015 expiry and the Rolled Over Dec 2015 expiry future contracts of EUA. The previous studies in this area have focused on a particular subset of EUA data and do not take care of the multicollinearities. We take EUA data from all three phases and the Rolled Over series, adopt principal component analysis to eliminate multicollinearities and then fit GARCH models for comprehensive analysis. The study establishes that the best models for predicting EUA phase I, II, III and Rolled Over series are asymmetric GARCH models.

Forecasting volatility of carbon under EU ETS: a multi-phase study

Many patients requiring plasmapheresis (PE) have renal failure and also need hemodialysis. If done separately almost 6-7 h is required. Hence, we decided to perform the procedures simultaneously in those patients requiring both PE and hemodialysis. The plasmafilter was inserted into the extracorporeal circuit after the hemodialyzer. A total of 8 such sessions of tandem PE and hemodialysis were performed in 2 patients. This is called tandem PE/hemodialysis. The total procedure was completed in the same time as is required for routine hemodialysis. The total amount of priming fluid is also less when PE and hemodialysis are performed separately. Thus, it is economically beneficial to the hospital and also convenient to the patient. Apart from transient episodes of hypotension, which were corrected by saline infusion, no other complications were noted.

Tandem plasmapheresis and hemodialysis.

Purpose – The purpose of this paper is to assess the informational efficiency of SP therefore, these are indicative of the violation of efficient market hypothesis in the case of S&P CNX Nifty index options market in India.Practical implications – The fi...

P.K. Jain

Papers

Prevention of thalassemia: a necessity in India.

Prenatal diagnosis of β‐thalassaemia: experience in a developing country

Forecasting volatility of carbon under EU ETS: a multi-phase study

Tandem plasmapheresis and hemodialysis.

Informational efficiency of implied volatilities of S&P CNX Nifty index options: A study in Indian securities market