Insulin resistance (IR) is a major factor in the pathogenesis of sepsis. Critically ill patients with multi-organ dysfunction syndrome (MODS), diagnosed as per modified Acute Physiology and Chronic Health Evaluation II (modified APACHE II) score criteria and admitted to the medical ward in our hospital, were assessed for IR and beta cell function by using the homeostasis model assessment A (HOMA-A) and HOMA-B models, respectively. Of 80 consecutive patients, 60 were followed up to day 7; 16 patients died and 4 did not agree to follow up. The mean value of IR in all the 80 patients studied on the day 1 of hospitalization was 6.67 +/- 10.65. The initial high values of serum insulin and IR were significantly reduced (p < 0.05) as these patients recovered from their critical illness. Of those who died, the first day mean insulin levels were high (13.80 +/- 14.72 micro/ml as well as IR 5.14 +/- 6.76 values), but they had statistically low beta cell function (46.45 +/- 433.64%) as compared to those who recovered (227.60 +/- 430.36%; p < 0.05). This suggests that, beta cell overexhaustion occurs in critically ill patients, because it was required to overcome the prevailing state of IR and has more bearing in patients having less than 4 organ failures. beta cell failure ensued from the onset in those who were more moribund and had more than four organs failing or those who died. IR and beta cell function are reliable indicators of the state of severity of critical illness, and they corroborated with mortality in patients with MODS.
In this report, the spectrum of -thalassemia mutations and genotype-to-phenotype correlations were defined in large number of patients (-thalassemia carriers and major) with varying disease severity in an Eastern Indian population mainly from the state of West Bengal. The five most common -thalassemia mutations were detected, which included IVS1-5 (G➝C), codon 15 (G➝A), codon 26 (G➝A), codon 30 (G➝C), and codon 41/42 (−TCTT). These accounted for 85% in 80 -thalassemic alleles deciphered from 56 patients, including -thalassemia major and carriers, and 15% of alleles remained uncharacterized in these patients. Expression of the human -globin gene is regulated by an array of cis-acting DNA elements, including five DNase I hypersensitive sites (HSs) in the locus control region (LCR), promoters that incorporate certain silencer elements, and enhancers at 3 of the -globin gene. For detailed studies and to understand the molecular basis of -thalassemia, we studied two groups of subjects: a group of 12 patients from four families having -thalassemia major and carrier phenotype and a control group of 26 healthy individuals. In these two groups, we examined portions of the -globin gene locus control region HSs 1, 2, 3, and 4, which included the (CA) x (TA) y repeat motif, the (AT) x N y (AT) z repeat motif, the inverted repeat sequence TGGGGACCCCA, the promoter region of the G ␥-globin gene, an (AT) x (T) y repeat 5 of the silencer region, and the -globin gene and its 3 flanking region. We investigated the allelic sequence polymorphisms in these regions and their association with the -thalassemia mutations to know the possible genotype-phenotype relationship in -thalassemia patients. An analysis of cisacting regulatory regions showed varied sequence haplotypes associated with some frequent -thalassemia mutations in this Eastern Indian population. Am.
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