Life expectancy and risk factors for early death in patients with severe thalassemia syndromes in South India.

In spite of advances in chelation therapy and screening of blood, mortality associated with the most common life-threatening noncommunicable disease of children in India, transfusion-dependent thalassemia (TDT), remains poorly defined. This study aims at estimating death rates and mortality risk factors associated with TDT. The clinical records of 1087 patients from 5 thalassemia centers in India were retrospectively analyzed from 2011 to 2018. Median patient age was 8.5 years, with 107 patients older than 18 years; 656 patients were male and 431 were female. Demographic details and clinical parameters were analyzed at presentation and at last visit. With 41 recorded deaths, actuarial survival at 26.9 years was 50%, and under-5 mortality was 7 times higher than in the general population. Patients with transfusion-transmitted infections (TTIs) had 3.4 times higher risk for death (P = .031). Serum ferritin higher than 4000 ng/dL had 4.6 times higher risk for mortality compared with ferritin lower than 1000 ng/dL (P = .00063). A hemoglobin drop lower than 2 g/dL per week had 7.7 times higher mortality risk compared with a drop of less than 1 g/dL per week (P < .0001). Social determinants (sex, economic status, and distance from center), splenectomy, and even cardiac complications were not associated with higher mortality risk. Main causes of death were infection, iron overload, TTIs, and allo-immunization. Patients who received more than 4 years of adequate care had more than 66% mortality risk reduction (P < .0001). TDT in India continues to result in high mortality. Ineffective transfusion, TTIs, and chelation continue to be the most significant risk factors. Comprehensive care in dedicated day care centers from early age is likely to improve outcomes.

Prevalence of Hypoparathyroidism (HPT) in Beta Thalassemia Major.

INTRODUCTION: The aim of this study was to assess the parathyroid functions and bone mineral density (BMD) in patients with beta thalassemia and to correlate them with serum ferritin, calcium, phosphorus and alkaline phosphatase levels. MATERIALS AND METHODS: This is a case control study which was done on 55 subjects (40 cases and 15 controls) in the age group of 2-18 years. The cases included were with confirmed diagnosis of beta thalassemia major, more than ten blood transfusions and serum ferritin levels >2000 µg/L irrespective of chelation therapy. RESULTS: Significant Hypoparathyroidism (HPT) observed along with low BMD levels in beta thalassemia patients (p < 0.01). A significant decrease in serum calcium level was seen in cases when compared to controls, where as the levels of both serum phosphorus and alkaline phosphatase levels increased in cases when compared to controls. CONCLUSION: BMD and PTH levels are very useful tools for diagnosing HPT. As a routine, in beta thalassemia major, screening for vitamin D deficiency and hypocalcemia should be done in second decade of life and as a preventive measure they should be supplemented with calcium and vitamin D to prevent hypocalcemic tetany, to facilitate bone growth and to prevent fractures.

Provocative poliomyelitis causing postpolio residual paralysis among select communities of two remote villages of North Karnataka in India: a community survey.

Intramuscular injections can provoke muscular paralysis especially, if the child has had exposure to polio virus. The purpose of the study was to determine the association with known risk factors for motor disabilities in two remote villages of North Karnataka (India), where an increased number of disabled people among select communities had been reported. A community based survey was conducted. The selection of study subjects was done through screening, history related with occurrence of musculoskeletal disability, screening and general examination of the affected joints and muscles. Data analysis was done by estimation of percentages. Among the physical disabilities identified, the most common was post-polio residual paralysis. 35.65% (n = 41) subjects had developed paralysis following the administration of an intramuscular injection when they had acute viremia in childhood, indicating that (probably) muscle paralysis would have been provoked by intramuscular injections, resulting in provocative poliomyelitis. Unnecessary injection must be avoided in children during acute viremia state and use of oral polio vaccine should be encouraged.

Immunogenicity and safety of Abhay M and M-vac vaccines in healthy infants: a phase III multicentric randomized single blind trial.

OBJECTIVE: To study immunogenicity and safety of Abhay M and M-Vac vaccines in prevention of measles in healthy infants. METHODS: In a randomized, single blind, comparative, multi-centric phase III trial, a total of 600 healthy infants between 9 - 15 months of age were recruited in the study from seven participating sites during five months. The block randomization design was used for randomizing the subjects into 2 vaccine groups (Investigational Vaccine - Abhay M and Control Vaccine - M-Vac) in the ratio 2:1. At base line (visit 1) a venous blood sample 1.5 ml was collected and subjects were then administered a single dose 0.5 ml of measles vaccine (Abhay M or M-Vac vaccine) subcutaneously according to randomization. Following administration of vaccine, subjects were observed closely for 30 - 60 minutes at the study hospitals for local reactions and systemic events. At visit 2 (follow up visit) another venous blood sample 1.5 ml was collected and the paired sera (both pre and post vaccination serum) were tested concurrently. Safety and immunogenicity were assessed through follow-up of adverse events and anti measles antibody response respectively. RESULTS: Overall 95.7 % seroconversion was achieved in both the groups, 96% in Abhay M vaccine group and 95.1%. in M-Vac vaccine group. There were no statistically significant differences in the observed seroconversion rates. In Abhay M vaccine group, the pre vaccination geometric mean titers (GMT) significantly increased from 35.5 mIU/ml to 486.9 mIU/ml after vaccination. The observed significant increase of GMT in M-Vac vaccine group was from 33.3 mIU/ml to 375.8 mIU/ml. Overall 459 (82.5%) out of 556 subjects were seroprotected after vaccination i.e. > or equal to [corrected] 200 mIU/ml (Protective levels). Of the 459 seroprotected, 315 (84.9%) subjects were in Abhay M vaccine group and 144 (77.8%) subjects were in M-Vac vaccine group. The frequencies of the reported local and general symptoms were similar between the Abhay M vaccine group and M-Vac vaccine group. CONCLUSION: Human Biologicals Institute's Abhay M vaccine is equally immunogenic and as safe as M-Vac vaccine when administered to healthy infants in single dose schedule.

Psedohypoparathyroidism in newborn - a rare presentation.

A 7-day-old male baby was referred with history of persistent multifocal convulsions from second day of life. He was found to have hypocalcemia, hyperphosphatemia, normal serum magnesium and normal renal function tests. Serum parathormone was found to be elevated. Baby was diagnosed as case of pseudohypoparathyroidism and was treated with calcium supplementation and calcitriol. At 9 months he was asymptomatic on treatment, with normal serum calcium and phosphorus.

Value of superficial cultures in diagnosing neonatal sepsis.

This study was conducted to determine the value of superficial cultures in the diagnosis of neonatal sepsis in our hospital. Sixty three babies, younger than 2 weeks who were admitted with suspected sepsis were investigated. A total of 369 cultures were obtained from these babies--252 (68.29%) superficial and 171 (31.70%) deep cultures. External ear canal swab, umbilical cord swab and throat swab culture accounted for the superficial cultures. Blood culture, cerebrospinal fluid culture and i.v. catheter culture accounted for deep cultures. Of the 369 cultures, 225 (60.97%) were positive for pathogens, which included Staphylococcus aureus, Klebsiella sp, Escherichia coli, Group B streptococcus and Enterococcus fecalis. The yield of pathogenic organisms was higher for superficial cultures (53.84%). All superficial cultures obtained during the study on each patient were simultaneously compared with the deep cultures by antimicrobial sensitivity method. The overall comparison showed that the practice of superficial cultures could be useful to predict the pathogenic organisms causing invasive disease.

Angiotensin II type 2 receptor-mediated apoptosis of cultured neurons from newborn rat brain.

Angiotensin II (Ang II) type 2 (AT2) receptors are highly expressed in neonate brain and may have a role in developmental processes such as apoptosis. Concurrent activation of c-Jun N-terminal kinase (JNK) and inhibition of Erk mitogen-activated protein kinase activities is important for apoptosis in many cells, and we previously demonstrated that stimulation of AT2 receptors causes decreased mitogen-activated protein kinase activity in neurons cultured from newborn rat hypothalamus and brain stem. Using such cultures we have employed terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling and internucleosomal DNA fragmentation to assess the role of AT2 receptors in neuronal apoptosis. Ang II (100 nM; 4-72 h) alone produced no significant neuronal apoptosis, and AT2 receptor activation did not stimulate JNK activity. However, exposure of cultures to UV radiation (6 J/m2/sec for 4 sec) to stimulate JNK elicited neuronal apoptosis that was significantly enhanced by Ang II, an effect that was abolished by the AT2 receptor antagonist PD 123,319 (1 microM) or the serine/threonine phosphatase inhibitor okadaic acid (3 nM). Additionally, Ang II enhanced the UV radiation-induced decrease in the levels of the DNA repair enzyme poly-(ADP-ribose) polymerase. These data indicate that Ang II, via AT2 receptors and activation of a serine/threonine phosphatase, contributes to neuronal apoptosis.

Modulation of angiotensin II type 2 receptor mRNA in rat hypothalamus and brainstem neuronal cultures by growth factors.

This study investigates the regulatory effects of growth factors upon angiotensin II type 2 (AT2) mRNA levels in neurons co-cultured from newborn rat hypothalamus and brainstem. Incubation of cultured neurons with nerve growth factor (NGF; 5-50 ng/ml) caused time-dependent changes in the steady-state levels of AT2 receptor mRNA. Short-term (0.5-1.0 h) incubations with NGF resulted in significant increases in AT2 receptor mRNA, whereas longer-term incubations (4-24 h) caused significant decreases. Activation of NGF receptors is known to stimulate phospholipase C-gamma and subsequently activate protein kinase C (PKC). Incubation of cultures with the PKC activator, phorbol-12-myristate-13-acetate (PMA; 100 nM), caused temporal changes in AT2 receptor mRNA levels similar to those observed with NGF. By contrast, insulin (0.1-10 microg/ml) elicited only significant decreases in AT2 receptor mRNA levels. The observed abilities of NGF and insulin to regulate the expression of AT2 receptor mRNA are consistent with the fact that the AT2 receptor gene promoter region contains several cis DNA regulatory elements that respond to growth factor-stimulated transcription factors. These novel observations which show that NGF and insulin can regulate AT2 receptor mRNA in neurons derived from neonatal rat CNS lend support to the idea that AT2 receptors have a role in development and differentiation.