Identification of Human Case of Avian Influenza A(H5N1) Infection, India.

A 11-year-old boy with acute myeloid leukemia was brought for treatment of severe acute respiratory infection in the National Capital Region, New Delhi, India. Avian influenza A(H5N1) infection was laboratory confirmed. Complete genome analysis indicated hemagglutinin gene clade 2.3.2.1a. We found the strain to be susceptible to amantadine and neuraminidase inhibitors.

Ocular kinetics and safety of intravitreally injected angiotensin converting enzyme inhibitor lisinopril.

BACKGROUND AND OBJECTIVES: The study investigated the intravitreal safety and vitreous disposition of lisinopril, an angiotensin converting enzyme inhibitor in rabbits for its projected use in retinopathy. METHODS: For the safety study, following the baseline ERG recording and fundus photography, 40 µg/50 µl of lisinopril sterile injection was injected unilaterally in the rabbit eyes (n = 4), where other eye served as a control. The electroretinogram and fundus images were obtained at 24, 48, 72 and 168 h following the intravitreal injection. For pharmacokinetics evaluation of the lisinopril, one eye of each rabbit (n = 4) received an intravitreal injection of lisinopril (40 µg/50 µl). The concentration of lisinopril in the ocular tissues, humours, plasma, lung, kidney and liver were measured through ESI-LC-MS/MS. RESULTS: Upon the electroretinography studies, no significant difference was observed in the ERG pattern in the lisinopril injected eye when compared to the baseline of the respective animals till the 7th day of the study. In the fundus imaging, no morphological changes were observed in the retina of the animal. The concentration of the lisinopril was found to be above to the IC50 in the retina-choroid till 36 h. The concentration found in the plasma and body tissues were many folds less than the IC50 of the lisinopril. CONCLUSIONS: Intravitreal injection of 40 µg/50 µl of lisinopril found to be safe in the rabbit eye as evidenced by the electroretinography and fundus imaging studies. The average half-life of lisinopril is 12.6 h and the above-mentioned dose able to sustain its IC50 value till the 36 h.

Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention.

OBJECTIVE: Examining the Retinal Renin Angiotensin System (RRAS) in the ROP neonates and analyzing the possibility of modulating the RRAS to prevent the progression in Oxygen Induced Retinopathy (OIR) model. METHOD: Vitreous of ROP patients (n = 44, median age 5.5 months) was quantified for RRAS components, VEGF, HIF-1α and compared with age matched control. The involvement of RRAS in ROP was tested in the rat model of OIR and compared with normoxia. Expressions of RAS components, VEGF and HIF-1α in retina were analyzed using qPCR and retinal structure and function was also analyzed. Effect of Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) was evaluated and compared with Bevacizumab which served as a positive control. Drug penetration into retina was confirmed by liquid chromatography coupled ESI-tandem mass spectroscopy (LC-MS/MS). RESULTS: Multifold increase in the expression of RAS components in human vitreous and rat retina showed their involvement in ROP. ERG & fundus studies in OIR revealed the altered function of retina and were successfully prevented by ARB (telmisartan), ACEI (lisinopril) and bevacizumab. Retinal analysis revealed the presence of ACEI and ARB in their therapeutic levels. CONCLUSION: This study for the first time demonstrates the upregulated level of RAS components in human ROP vitreous and further that the pharmacological intervention in RRAS can functionally and structurally preserve retina against the progression of ROP in the OIR model.

Topical Oil Application and Trans-Epidermal Water Loss in Preterm Very Low Birth Weight Infants-A Randomized Trial.

OBJECTIVE: Topical emollient application reduces trans-epidermal water loss (TEWL) in preterm neonates. Coconut oil used traditionally for infant massage in India has not been evaluated for the same. PATIENTS AND METHODS: Very low birth weight (VLBW) neonates were randomized at 12 h of age to Oil (n = 37) or Control (n = 37) groups. Oil group neonates received twice-daily coconut oil application without massage, and Control group received standard care. TEWL was measured every 12 h using an evaporimeter till Day 7 when skin swabs were obtained for bacterial growth and skin condition was assessed using a validated score. RESULTS: Birth weight (g; mean ± SD: 1213 + 214 vs. 1164 + 208, p = 0.31), gestation [week; median (interquartile range): 32 (31-33) vs. 32 (29-33), p = 0.10] and other baseline variables were comparable. TEWL was significantly reduced (g/m(2)/h, mean difference: -6.80, 95% confidence interval: -3.48, -10.15; p < 0.01) with better skin condition and lower bacterial growth in the Oil group (20% vs. 60%, p < 0.01). CONCLUSION: Coconut oil application reduced TEWL without increasing skin colonization in VLBW neonates. CLINICAL TRIALS REGISTRATION: NCT01758068.

Efficacy of zinc in reducing hyperbilirubinemia among at-risk neonates: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of oral zinc salt on the incidence of hyperbilirubinemia and need for phototherapy between 25 and 168 h of age in term and late-preterm at-risk neonates cared at a tertiary care hospital in New Delhi, India. METHODS: In all neonates born at ≥35 wks' gestation, serum total bilirubin (STB) was assayed at 24 ± 6 h of age. At-risk neonates, neonates with STB levels ≥6 mg/dL, were given either 10 mg of zinc gluconate salt (n = 148) or placebo (n = 146) in twice daily doses till day seven of age. Jaundice was assessed clinically and STB was measured by spectrophotometry. Neonates were followed up until day seven of age. Primary outcome measure was incidence of hyperbilirubinemia (STB ≥ 15 mg/dl). Secondary outcome measures were mean STB level at 72 ± 12 h of age, proportion of infants requiring phototherapy, and duration there of. RESULTS: Risk factors for hyperbilirubinemia, including male gender, gestational age, birth-weight, incidence of birth trauma, ABO incompatibility, hyperbilirubinemia in previous sib, etc. were comparable in zinc and placebo groups. The incidence of hyperbilirubinemia was comparable in both the groups (17.9% vs 19.1% in zinc and placebo groups respectively; OR = 0.95, 95% CI: 0.50 to 1.67; P = 0.92). The requirement of phototherapy (14.5% and 12.0% in zinc and placebo groups respectively; OR = 1.24, 95% CI: 0.95 to 2.6; P = 0.54) was comparable in both the groups; however, duration of phototherapy was shorter in zinc group (duration in hours, 22.8 ± 19.4 vs 35.6 ± 16.1 in zinc and placebo group respectively; mean difference = -12.8, 95% CI: -24.73 to -0.92; P = 0.04). There was no difference in the mean STB levels at 72 ± 12 h of age between zinc and placebo groups (mean difference in mg/dL: 0.20, 95% CI: 1.0 to -0.64). No significant adverse effects related to oral zinc administration were noted. CONCLUSIONS: Twice daily administration of oral zinc in a dose of 10 mg/day does not reduce the incidence of hyperbilirubinemia in at-risk term and late-preterm neonates during first wk of age.

Transcutaneous bilirubin levels in healthy term and late preterm Indian neonates.

OBJECTIVE: To provide normative data for transcutaneous bilirubin (TcB) measurements in healthy term and late-preterm Indian neonates during first 72 h of age using a multiwavelength reflectance transcutaneous bilimeter. METHODS: TcB measurements were performed in healthy neonates (gestation 35 wk), in a well-baby ward, using a multiwavelength transcutaneous bilimeter (BiliCheck, SpectRx Inc, Norcross, GA). Age-specific percentiles values for each 6-h epoch starting at 0 h of age were calculated and an age-specific TcB nomogram was developed using different percentile values. Diagnostic ability of each percentile curve for prediction of hyperbilirubinemia, defined as requirement of phototherapy, was calculated. RESULTS: We performed 925 TcB measurements on 625 healthy newborn infants (gestation: 35 to 41 wk; age: 0 to 72 h; mean birth weight: 2808+/-437 g). TcB increased in a linear manner with maximum rate of rise observed during first 24 h of age (50th percentile: 0.22 mg/dL/h). 50th percentile curve of age-specific TcB nomogram had high negative predictive value (99.8%) and acceptable positive predictive value (16.4%) for prediction of hyperbilirubinemia. CONCLUSION: We provided age-specific nomogram of TcB for first 72 h of age in healthy term and late-preterm Indian neonates. Percentile curves and rate of rise in TcB may help in identification of neonates at low-risk of development of hyperbilirubinemia facilitating their safer discharge from the hospital. Diagnostic utility of this nomogram for predicting hyperbilirubinemia needs to be tested in a separate validation cohort.

Does measuring the changes in TcB value offer better prediction of Hyperbilirubinemia in healthy neonates?

OBJECTIVE: We evaluated the diagnostic value of changes in transcutaneous bilirubin (TcB) levels for prediction of subsequent hyperbilirubinemia in healthy term and late-preterm neonates. METHODS: Neonates at 35 weeks of gestation were enrolled in a prospective study. Two TcB determinations were performed for all enrolled neonates (N = 358). The first assessment (TcB(1)) was performed at 24 +/- 6 hours of age, followed by a second (TcB(2)) >or=12 hours later. Changes in TcB levels were calculated. TcB values were plotted on an hour-specific serum bilirubin nomogram, and risk zones were recorded. Of the 358 neonates enrolled, 325 neonates (91%) were monitored for hyperbilirubinemia until 5 days of age. RESULTS: The mean ages of TcB(1) and TcB(2) estimations were 23 +/- 4 hours and 42 +/- 4 hours, respectively. A total of 14.9% of neonates (48 of 325 neonates) developed hyperbilirubinemia by 5 days of age. The sensitivity, specificity, and positive and negative likelihood ratios for prediction of subsequent hyperbilirubinemia for TcB(1) (zone >2, >75th percentile) were 80.4%, 58.0%, 1.9, and 0.34; those for TcB(2) (zone >2, >75th percentile) were 82.6%, 79.0%, 4.0, and 0.22; and those for the change in TcB levels (>0.18 mg/dL per hour, >75th percentile) were 82.5%, 82.9%, 4.8, and 0.21, respectively. Gestational age, TcB risk zone, and change in TcB levels were found to be independent predictors of subsequent hyperbilirubinemia. CONCLUSIONS: Single TcB measurements at 30 to 48 hours predict hyperbilirubinemia with a reasonably high degree of accuracy. Changes in TcB levels do not offer any added clinical benefit.

Congenital cytomegalovirus infection in a highly seropositive semi-urban population in India.

To determine the incidence and natural history of congenital cytomegalovirus (CMV) infection in a population of women with near universal serologic reactivity for CMV, a prospective study of 423 women attending the antenatal clinic of the Comprehensive Rural Health Center in northern India was conducted. All 9 (2.1%) CMV positive infants were born to mothers who were CMV seropositive at the first antenatal visit. One child had hepatosplenomegaly at birth and another child had mild unilateral hearing loss at 4 months of age.

Carrier frequency of F508del mutation of cystic fibrosis in Indian population.

BACKGROUND: Cystic fibrosis (CF) is considered to be very rare in Indian subcontinent. Based on reports of CF in migrants from Indian subcontinent to United Kingdom and United States of America, the prevalence of CF is estimated to be between 1/10,000 and 1/40,000 in this ethnic group. The present study was done to estimate the carrier frequency of F508del mutation among neonates using cord blood samples to reflect the prevalence of CF in the study population. METHODS: 955 mothers delivering at our hospital between December 1999 and November 2000 were enrolled. Cord blood samples were analyzed for F508del mutation using polymerase chain reaction and gel electrophoresis. The frequency of patients homozygous for F508del mutation in the population was estimated using Hardy-Weinberg principle. The prevalence of CF was estimated by using the proportion of F508del homozygous cases out of all CF patients, as reported in various studies (19-44%) from Indian subcontinent. RESULTS: Out of 955 cord blood samples, 4 were positive for F508del mutation. The carrier frequency and gene frequency of F508del mutation in the Indian population was calculated to be 1/238 (0.42%) and 1/477 (0.21%), respectively. Frequency of CF patients homozygous for F508del mutation is 1/228,006. The estimated prevalence of CF is 1/43,321 to 1/100,323 in Indian population. CONCLUSION: CF does occur in Indian subcontinent though the prevalence is lesser than the Caucasian population.