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Biomedical subjects

A Singhal

Publications and source records attributed to A Singhal.

At least 37 records · Page 2Linked to original sources
PubMed2001

Apnea in the newborn.

Apnea, defined as cessation of breathing resulting in pathological changes in heart rate and oxygen saturation, is a common occurrence in sick neonates. Apnea is a common manifestation of various etiologies in sick neonates. In preterm children it may be related to the immaturity of the central nervous system. Secondary causes of apnea should be excluded before a diagnosis of apnea of prematurity is made. Methylaxanthines and Continuous Positive Airway Pressure form the mainstay of treatment of apnea in neonates. Mechanical ventilation is reserved for apnea resistant to above therapy. An approach to the management of apnea in neonates has been described.

Aminophylline↗
PubMed2001

Catch-up growth in small-for-gestational-age term infants: a randomized trial.

BACKGROUND: Small-for-gestational-age (SGA) term infants are at risk of long-term growth deficits. OBJECTIVE: The objectives were to test the hypothesis that postnatal growth in SGA term infants can be altered by dietary intervention and to examine whether there is a critical window for nutritional programming of the growth trajectory during the first 9 mo postnatally. DESIGN: Healthy term (gestation > or =37 wk) infants with birth weights below the 10th centile were randomly assigned to receive standard term formula (TF; n = 147) or nutrient-enriched formula (EF; n = 152) for the first 9 mo; 175 breast-fed SGA term infants formed a reference group. The main outcome measures were weight, length, and occipitofrontal head circumference (OFC) at 9 and 18 mo. RESULTS: The infants fed the EF showed greater gains in length by 9 (1.1 cm; 95% CI: 0.38, 1.79) and 18 (1.0 cm; 0.25, 1.83) mo and in OFC by 9 (0.5 cm; 0.1, 0.9) and 18 (0.6 cm; 0.2, 1.1) mo than did infants fed the TF; the differences were larger in females. The dietary effects were independent of the pattern of growth retardation. Breast-fed infants showed greater gains in weight and OFC by 18 mo than did infants fed the TF; however, these differences disappeared after adjustment for age, parental size, and birth order. CONCLUSIONS: Linear growth and OFC gains in SGA term infants improve after nutritional intervention during the first 9 mo of life and the effects persist for > or =9 mo beyond the intervention period. Further information on whether catch-up growth is beneficial or detrimental to long-term outcomes is required before public health interventions can be recommended.

Analysis of Variance↗
PubMed2001

Sickle cell disease and age at menarche in Jamaican girls: observations from a cohort study.

AIMS: (1) To investigate the distribution of age at menarche in a representative sample of 99 patients with homozygous sickle cell (SS) disease, 69 with sickle cell haemoglobin C (SC) disease, and 100 controls with a normal haemoglobin (AA) genotype followed in a cohort study from birth. (2) To explore the determinants of the age at menarche. METHODS: Children ascertained in a newborn screening programme were followed prospectively from birth to age 18-26.5 years with regular assessments of height, weight, pubertal stage, and haematological indices at the Sickle Cell Clinic of the University Hospital of the West Indies. RESULTS: All subjects have now reached menarche and the mean age in normal controls (13.0 years) was significantly earlier than in SC disease (13.5 years) or SS disease (15.4 years). Greater weight and earlier age at menarche was the only association significant across all genotypes although additional contributions occurred from fetal haemoglobin and red cell count in SS disease. Alpha thalassaemia, which ameliorates many of the effects of SS disease, had no discernible effect on menarche. CONCLUSIONS: Mean age at menarche is delayed by 0.5 years in SC disease and by 2.4 years in SS disease. Weight appears to be the principle determinant of age at menarche.

Adolescent↗
PubMed2001

Randomized trial comparing the efficacy of a novel manual breast pump with a standard electric breast pump in mothers who delivered preterm infants.

OBJECTIVE: The benefits of human milk for preterm infants are widely recognized, yet technological advances in milk expression have been slow. We compared the efficacy of a standard electric pump (EP; Egnell) used in 94% of United Kingdom neonatal units with a novel manual pump (MP; Avent ISIS) designed to operate more physiologically by simulating the infant's compressive action on the areola during breastfeeding. METHODS: We randomized 145 women who delivered infants of <35 weeks' gestation to use the MP or the EP and measured total milk volume expressed while using the randomized pump during the infant's hospital stay, pattern of milk output and creamatocrit of milk expressed during a test period in the second week, and pump characteristics by maternal questionnaire. RESULTS: Mothers who used the EP, who frequently double pumped, showed shorter expression times but produced no more milk than mothers who used the MP. When both pumped sequentially, however, mothers who used the MP showed significantly greater milk flow and total volume over 20 minutes. Creamatocrit was unaffected by pump type. The MP was rated significantly higher than the EP on 5 major characteristics. CONCLUSIONS: When compared on equal terms (sequential pumping), mothers who used the MP showed greater milk flow, perhaps reflecting more physiologic pump design. Even with double pumping, mothers who used the EP did not advantage their infants with greater milk production. We believe that this novel, effective MP, preferred by mothers and costing a fraction of the EP price, reflects a significant advance in milk expression for high-risk infants.breast pumps, randomized trial, preterm infants.

Breast↗
PubMed2001

Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants.

OBJECTIVES: Preterm infants are frequently discharged from the hospital growth retarded and show reduced growth throughout childhood. In a large efficacy and safety trial, we tested the hypothesis that nutritional intervention in the first 9 months postterm would reverse postdischarge growth deficits and improve neurodevelopment without adverse safety outcomes. PARTICIPANTS AND INTERVENTION: Two hundred eighty-four infants (mean gestation: 30.9 weeks) were studied; 229 were randomly assigned a protein, energy, mineral, and micronutrient-enriched postdischarge formula (PDF; N = 113) or standard term formula (TF; N = 116) from discharge (mean 36.5 weeks' postmenstrual age). A reference group (N = 65) was breastfed until at least 6 weeks' postterm. Outcome measures. Anthropometry was performed at 6 weeks and 3, 6, 9, and 18 months. Development was measured at 9 months (Knobloch, Passamanick, and Sherrard's developmental screening inventory) and 18 months (Bayley Scales of Infant Development II; primary outcome) postterm. RESULTS: At 9 months, compared with the TF group, those fed PDF were heavier (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (difference 1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 months (difference 0.82 cm; 95% CI: -0.04-1.7). There was no effect on head circumference. The effect of diet was greatest in males; at 9 months length deficit with TF was 1.5cm (95% CI: 0.3-2.7), and this remained at 18 months (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in developmental scores at 9 or 18 months, although PDF infants had a 2.8 (-1.3-6.8) point advantage in Bayley motor score scales. At 6 weeks' postterm, exclusively breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6cm (95% CI: 0.8-2.3) shorter than the PDF group, and they remained smaller up to 9 months' postterm. CONCLUSIONS: 1) Improving postdischarge nutrition in the first 9 months may "reset" subsequent growth-at least until 18 months for body length. We intend to follow-up the children at older ages. The observed efficacy of PDF was not associated with adverse safety outcomes. 2) We cannot reject the hypothesis that postdischarge nutrition benefits motor development and this requires additional study. 3) Our data raise the possibility that breastfed postdischarge preterm infants may require nutritional supplementation, currently under investigation.

Anthropometry↗
PubMed2001

Lemierre's syndrome.

We describe a 32-year-old woman who had temperatures increasing over 7 days from 100.7 degrees F to 104.0 degrees F. She had an upper respiratory infection and swelling of the left side of the neck. She was diagnosed with Lemierre's syndrome.

Acute Disease↗
PubMed2000

Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes.

PURPOSE: To design, synthesize, and test synthetic glycopeptide-based delivery systems for gene targeting to hepatocytes by systemic administration. METHODS: All peptides were synthesized by the solid phase method developed using Fmoc chemistry on a peptide synthesizer. The binding of galactosylated peptides to HepG2 cells and accessibility of the galactose residues on particle surface was demonstrated by a competition assay using 125I-labeled asialoorosomucoid and RCA lectin agglutination assay, respectively. DNA plasmid encoding chloramphenicol acetyl transferase (CAT) gene was complexed with a tri-galactosylated peptide (GM245.3) or tri-galactosylated lipopeptide (GM246.3) in the presence of an endosomolytic peptide (GM225.1) or endosomolytic lipopeptide (GM227.3) to obtain DNA particles of 100-150 nm in size. The plasmid/peptide complexes were added to HepG2 cell cultures or intravenously administered by tail vein injection into normal mice or rats. Plasmid uptake and expression was quantified by qPCR and ELISA, respectively. RESULTS: Multiple antennary glycopeptides that have the ability to condense and deliver DNA plasmid to hepatocytes were synthesized and complexed with DNA plasmid to obtain colloidally stable DNA/peptide complexes. Addition of DNA/GM245.3/GM225.1 peptide complexes (1:3:1 (-/+/-)) to HepG2 cell cultures yielded CAT expression in transfected cells. The transfection efficiency was significantly reduced in the absence of galactose ligand or removal of endosomolytic peptide. Intravenous administration of DNA/GM245.3 peptide complexes (1:0.5 (-/+)) into the tail vein of normal rats yielded DNA uptake in the liver. Substitution of GM245.3 by galactosylated lipopeptide GM246.3 resulted in more stable DNA particles, and a 10-fold enhancement in liver plasmid uptake. CAT expression was detectable in liver following intravenous administration of DNA/GM246.3 complexes. Addition of endosomolytic lipopeptide GM227.3 into the complexes (DNA/ GM246.3/GM227.3 (1:0.5:1 (-/+/-))) yielded a 5-fold increase in CAT expression. Liver expression was 8-fold and 40-fold higher than lung and spleen, respectively, and localized in the hepatocytes only. The transfection efficiency in liver was enhanced by increasing DNA dose and injection volume. The plasmid uptake and expression in liver using DNA/GM246.3/GM227.3 complexes was 100-200-fold higher than DNA formulated in glucose. Tissue examination and serum biochemistry did not show any adverse effect of the DNA/GM246.3/ GM227.3 (1:0.5:1 (-/+/-)) complexes after intravenous delivery. CONCLUSIONS: Gene targeting to hepatocytes was achieved by systemic administration of a well-tolerated synthetic glycopeptide-based delivery system. The transfection efficiency of this glycopeptide delivery system was dependent on peptide structure, endosomolytic activity, colloidal particle stability, and injection volume.

Amino Acid Sequence↗
PubMed2000

Entertainment-education and HIV/AIDS prevention: a field experiment in Tanzania.

Entertainment-education is the process of designing and implementing an entertainment program to increase audience members' knowledge about a social issue, create more favorable attitudes, and change their overt behaviors regarding the social issue. The results of a field experiment in Tanzania to measure the effects of a long-running entertainment-education radio soap opera, Twende na Wakati (Let's Go with the Times), on knowledge, attitudes, and adoption of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) prevention behaviors are presented. Multiple independent measures of effects and the experimental design of this study confer strong internal and external validity regarding the results of this investigation. The effects of the radio program in Tanzania include (1) a reduction in the number of sexual partners by both men and women, and (2) increased condom adoption. The radio soap opera influenced these behavioral variables through certain intervening variables, including (1) self-perception of risk of contracting HIV/AIDS, (2) self-efficacy with respect to preventing HIV/AIDS, (3) interpersonal communication about HIV/AIDS, and (4) identification with, and role modeling of, the primary characters in the radio soap opera.

Adolescent↗
PubMed2000

Determining the physical limits of the Brassica S locus by recombinational analysis.

A genetic analysis was performed to study the frequency of recombination for intervals across the Brassica S locus region. No recombination was observed between the S locus glycoprotein gene and the S receptor kinase gene in the segregating populations that we analyzed. However, a number of recombination breakpoints in regions flanking these genes were identified, allowing the construction of an integrated genetic and physical map of the genomic region encompassing one S haplotype. We identified, based on the pollination phenotype of plants homozygous for recombinant S haplotypes, a 50-kb region that encompasses all specificity functions in the S haplotype that we analyzed. Mechanisms that might operate to preserve the tight linkage of self-incompatibility specificity genes within the S locus complex are discussed in light of the relatively uniform recombination frequencies that we observed across the S locus region and of the structural heteromorphisms that characterize different S haplotypes.

Brassica↗
PubMed2000

Height and weight reference curves for homozygous sickle cell disease.

OBJECTIVE: To derive height and weight growth reference curves for children with homozygous sickle cell disease. STUDY DESIGN: Subjects (n = 315) were participants in a population based, longitudinal cohort study of sickle cell disease in Kingston, Jamaica. Regular measurements of height and weight were made from enrollment into the study at birth up to 22 years of age. RESULTS: Sex specific growth reference curves for height for age and weight for age covering the age range 0-18 years are presented. CONCLUSION: These growth reference curves are suitable for identifying coincidental growth problems in children with homozygous sickle cell disease.

Adolescent↗
PubMed2000

Clinical safety of iron-fortified formulas.

BACKGROUND: Iron-fortified formulas are recommended throughout infancy and are frequently used beyond, yet safety aspects have been inadequately studied. Iron could theoretically increase pro-oxidant stress, with potential adverse effects, including infection risk, and some clinicians suspect that iron-fortified formulas induce gastrointestinal disturbance. OBJECTIVE: A planned component of a large intervention trial has been to test the hypothesis that infants receiving iron-fortified formula do not have a higher incidence of infections (primary outcome) or gastrointestinal problems (secondary outcome) than infants on low iron-formulas or cow's milk. Methods. Children (n = 493) 9 months old receiving cow's milk were recruited in 3 UK centers and randomized to: 1) cow's milk as before, 2) formula containing.9 mg/L of iron, or 3) an otherwise identical formula but containing 12 mg/L of iron. Children were followed at 3 monthly intervals and the episodes of infections, diarrhea and constipation, and general morbidity to 18 months old were recorded. Hematologic indices of iron status were determined at 18 months old. RESULTS: Serum ferritin concentrations were increased in infants receiving iron-fortified formula but there were no intergroup differences in incidence of infection, gastrointestinal problems, or in general morbidity or weight gain. CONCLUSIONS: We were unable to identify adverse health effects in older infants and toddlers consuming a high iron-containing formula (12 mg/L) even when used in populations with a low incidence of iron deficiency.

Animals↗
PubMed1999

Intratracheal administration of interleukin 12 plasmid-cationic lipid complexes inhibits murine lung metastases.

Administration of plasmid/lipid complexes to the lung airways for the treatment of metastatic pulmonary diseases represents a new strategy of gene therapy. In this study we present evidence that intratracheal administration of a plasmid encoding murine IL-12 complexed with N-[1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride:cholesterol inhibits the growth of lung metastases, using a renal cell carcinoma model. Instillation of pIL-12/lipid complexes resulted in expression of biologically active IL-12 (170-240 pg/ml) and IFN-gamma (100-190 pg/ml) in the bronchoalveolar lavage fluid. A significantly reduced number of lung metastases (26+/-24) was observed in mice instilled with IL-12/lipid complexes 24 hr after tumor challenge, whereas more than 250 metastatic foci were counted in lungs of untreated mice. Moreover, IL-12/lipid inhibited the growth of 3-day-old established metastases when compared with empty plasmid/lipid or IL-12 plasmid in saline. Mice receiving IL-12 gene therapy survived significantly longer (median survival of 43 days) than untreated mice (median survival of 31 days) or mice treated with control plasmid/lipid complexes (median survival of 35 days). These data demonstrate that a nonviral IL-12 gene therapy employing synthetic cationic lipids as a delivery system can be used to inhibit the development of lung metastases. Thus, this method provides support for the use of IL-12/lipid complexes to control the growth of pulmonary metastases and represents a potentially safer alternative to IL-12 protein immunotherapy.

Animals↗
PubMed1999

Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of angiostatic factors should be a viable approach for cancer gene therapy. Endostatin, a potent angiostatic factor, was expressed in mouse muscle and secreted into the bloodstream for up to 2 weeks after a single intramuscular administration of the endostatin gene. The biological activity of the expressed endostatin was demonstrated by its ability to inhibit systemic angiogenesis. Moreover, the sustained production of endostatin by intramuscular gene therapy inhibited both the growth of primary tumors and the development of metastatic lesions. These results demonstrate the potential utility of intramuscular delivery of an antiangiogenic gene for treatment of disseminated cancers.

Animals↗
PubMed1999

Analgesia, pruritus, and ventilation exhibit a dose-response relationship in parturients receiving intrathecal fentanyl during labor.

UNLABELLED: Several studies have characterized the 50% and 95% effective doses (ED50 and ED95, respectively) of intrathecal sufentanil for labor analgesia. Few have investigated these same criteria for the less expensive alternative, fentanyl. In addition, the ventilatory effects of intrathecal fentanyl at clinically relevant doses are unclear. We performed this study to establish the dose-response relationship of intrathecal fentanyl for both analgesia and ventilatory depression. Ninety parturients in active early labor (< or = 5 cm dilation) received intrathecal fentanyl 5, 7.5, 10, 15, 20, or 25 micrograms in a double-blinded, randomized fashion (n = 15 patients in each group). Parturients were monitored for degree of pain (measured using a 100-mm visual analog pain scale), blood pressure, arterial oxygen saturation (SaO2), respiratory rate, ETCO2, and fetal heart rate 0, 1, 5, 10, 15, 20, 25, and 30 min after the administration of intrathecal fentanyl. An absolute visual analog pain scale score < or = 25 mm was defined a priori as analgesic success. The percentage of parturients who achieved analgesic success was used to construct quantal dose-response curves, from which the ED50 and ED95 values were derived for the total population (mixed parity) and the nulliparous and multiparous subpopulations separately. Overall ED50 and ED95 values (95% CI) were 5.5 (3.4-7.2) and 17.4 (13.8-27.1) micrograms, respectively. Nulliparous values were lower (5.3 and 15.9 micrograms, respectively) than multiparous values (6.9 and 26.0 micrograms, respectively) but were within the 95% CIs of the total population. Pruritus incidence in parturients with analgesic success displayed a dose-response relationship identical to that seen for analgesia. ETCO2 displayed a dose-related increase, particularly at doses > or = 15 micrograms, without concomitant changes in respiratory rate or SaO2, which suggests a decrease in tidal volume. Even in the absence of overt signs or symptoms of somnolence, intrathecal fentanyl at doses within the effective analgesic range induced a change in ventilation that may last longer than the 30-min period we studied. IMPLICATIONS: Intrathecal fentanyl induces rapid and satisfying dose-dependent analgesia in early labor; however, it also produces dose-related decreases in ventilation in the absence of overt somnolence.

Adult↗