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Biomedical subjects

R Dhanireddy

Publications and source records attributed to R Dhanireddy.

At least 19 recordsLinked to original sources

Venous gangrene of lower extremities and Staphylococcus aureus sepsis.

This is a study of the venous gangrene of lower extremities and Staphylococcus aureus sepsis. We report on a premature infant who developed phlegmasia cerulea dolens (PCD) in both lower extremities in association with S. aureus sepsis, resulting in gangrene of the right foot. Non-pitting edema and cyanosis of the digits of the right lower extremity were noted 48 hours after hypotension and severe shock due to S. aureus sepsis. Intravenous antibiotics, isotonic fluids, and heparin were administered. Twenty-four hours later, edema and ischemic changes of the first and fifth left toes were also noted. Doppler flow study showed flow signals in both right and left popliteal arteries. However, there were no Doppler signals in neither right nor left popliteal vein. Emergency fasciotomies were performed on both lower limbs. The progression of the gangrene was limited to the right foot. There was complete resolution of PCD in both lower extremities. To the best of our knowledge, the association of S. aureus sepsis with PCD and venous gangrene in an infant has not been reported previously. This case illustrates the need for early recognition of PCD and aggressive intervention.

Foot Diseases↗

Association of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy of prematurity and progression to laser therapy in extremely low-birth-weight infants.

OBJECTIVE: The objective of this study was to evaluate the role of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy and progression to laser therapy. BACKGROUND: Postnatal steroids have been frequently used in the management of infants with chronic lung disease, airway edema, and hypotension, but their use is not free from adverse effects. Postnatal dexamethasone use has been associated with increased risk for the development of fungal sepsis, but the influence of glucocorticoid therapy on retinopathy of prematurity (ROP) is controversial. Candida sepsis has been shown to be associated with severe ROP and the need for laser therapy in some studies but not in others. STUDY DESIGN: Medical records of all <1000 g birth weight infants (n=158) admitted to Louisiana State University Health Sciences Center between July 1, 1996 and June 30, 1999 were reviewed. After exclusion of those infants who either died (n=25) or transferred (n=3) before eye examination, demographic and clinical data of 130 infants were analyzed by chi-squared analysis, Mann-Whitney U test, t-test, analysis of variance, and logistic regression. All data are mean+/-SD. RESULTS: Gestational age was 26.4+/-1.7 weeks; birth weight was 797+/-130 g. Twenty-six infants were Caucasian, the rest African-American. Seventy-five (58%) received antenatal steroids. Eighty-eight (68%) of the infants received postnatal steroids. All infants were exclusively fed premature infant formulae. Sepsis developed in 44 (34%) infants and fungal sepsis in 14 (11%). Incidence of ROP was 77% (100/130), severe ROP (stage > or =3) 52% (68). Severe ROP was more frequent in Caucasian infants (p=0.005) and in infants who received postnatal dexamethasone (p< or =0.0001). The development of threshold ROP (zone 1 or 2 with stage 3+, five contiguous or eight total clock hours of the retina) and requirement for laser therapy were higher in Caucasians (p=0.0002) and in infants with fungal sepsis (p=0.001). Antenatal steroids had no effect on the severity of ROP or the need for laser treatment. Postnatal dexamethasone use was significantly associated with fungal sepsis 13/14 (93%). After controlling for gestational age, race, days on supplemental oxygen, and fungal sepsis, cumulative postnatal dexamethasone use was independently associated with severe ROP [OR 1.2 (1.04-1.33)], and fungal sepsis [OR 8.2 (2.0-33.0)] was independently associated with the need for laser therapy. CONCLUSIONS: Postnatal steroid use is an independent risk factor for development of severe ROP. The risk of threshold ROP requiring laser treatment was higher in infants who developed fungal sepsis.

Analysis of Variance↗

Association of human milk feedings with a reduction in retinopathy of prematurity among very low birthweight infants.

INTRODUCTION: With the increased survival of very low birthweight (VLBW) infants, weighing less than 1500 g at birth, the incidence of retinopathy of prematurity (ROP), a significant cause of blindness among children in the United States, is also increasing. Preterm infants with a positive diagnosis of ROP during the perinatal period are at increased risk for ocular abnormalities and for deficits in visual function during later periods of development. Human milk has many antioxidant constituents including inositol, vitamin E, and beta-carotene that may protect against the development of ROP. OBJECTIVE: The objective of this study was to examine the effect of human milk feedings on the incidence of ROP among VLBW infants. STUDY DESIGN: Observational cohort study. PARTICIPANTS: We identified 283 VLBW infants admitted to the Georgetown University Medical Center Neonatal Intensive Care Unit (NICU) from January 1992 through September 1993. All infants surviving to receive enteral feeding and ophthalmologic examinations for ROP (n=174) were included in the analysis. METHODS: Type of feeding (human milk versus exclusive formula), presence of ROP, and potential confounding variables were abstracted retrospectively from medical records. ROP was present if any stage of ROP was diagnosed at any age during the initial NICU hospitalization; each case was counted once based on the worse severity of ROP in either eye. Multiple logistic regression was used to control for confounders. MAIN OUTCOME MEASURE: ROP. RESULTS: Major predictors of ROP were similar in both feeding groups including gestational age, days on mechanical ventilation, and total number of days on supplemental oxygen. The incidence of ROP differed significantly by type of feeding (human milk -41.0% vs. formula -63.5%, p=0.005). Human milk feeding independently correlated with a reduced odds of ROP (OR: 0.42, 95% CI: 0.19 to 0.93) (p=0.03), controlling for gestational age, duration of supplemental oxygen therapy, 5-minute Apgar score, and race. Human milk feeding independently correlated with a reduced odds of ROP (OR: 0.46, 95% CI: 0.18 to 0.91) (p=0.03), controlling for birthweight, duration of supplemental oxygen therapy, 5-minute Apgar score, and race. CONCLUSION: Human milk feeding among VLBW infants was associated with a lower incidence of ROP compared to exclusively formula-fed VLBW infants after adjusting for confounding variables.

Apgar Score↗

Placental transfusion: umbilical cord clamping and preterm infants.

OBJECTIVE: To investigate the clinical effects of early versus late cord clamping in preterm infants. STUDY DESIGN: A total of 32 premature infants were prospectively randomized. The following parameters were measured: Initial spun hematocrit (Hct), hemoglobin (Hgb), red blood cell (RBC) counts, frequency of blood transfusions, peak serum bilirubin, mean blood pressure (MBP), oxygen index, intraventricular hemorrhage, and significant patent ductus arteriosus (PDA). RESULTS: Over the 4-week study period, the delayed cord clamping (DCC) group exhibited a decrease in the frequency of blood transfusion (p < 0.001) and also a decrease in albumin transfusions over the first 24 hours (p < 0.03). MBP in the first 4 hours was higher in the DCC group (p < 0.01), and there were statistically significant increases in Hct (21%), Hgb (23%), and RBC count (21%) compared with the early cord clamping group. The risks of patent ductus arteriosus, hyperbilirubinemia, or intraventricular hemorrhage were similar in both groups. Late clamping of the umbilical cord had little or no effect on the oxygen index. CONCLUSION: DCC significantly reduced the requirement for blood and albumin transfusion. It also increased the initial Hct, RBC count, Hgb levels, and MBP.

Blood Component Transfusion↗

A comparison of neonatal mortality risk prediction models in very low birth weight infants.

BACKGROUND: Risk-adjusted severity of illness is frequently used in clinical research and quality assessments. Although there are multiple methods designed for neonates, they have been infrequently compared and some have not been assessed in large samples of very low birth weight (VLBW; <1500 g) infants. OBJECTIVES: To test and compare published neonatal mortality prediction models, including Clinical Risk Index for Babies (CRIB), Score for Neonatal Acute Physiology (SNAP), SNAP-Perinatal Extension (SNAP-PE), Neonatal Therapeutic Interventions Scoring System, the National Institute of Child Health and Human Development (NICHD) network model, and other individual admission factors such as birth weight, low Apgar score (<7 at 5 minutes), and small for gestational age status in a cohort of VLBW infants from the Washington, DC area. METHODS: Data were collected on 476 VLBW infants admitted to 8 neonatal intensive care units between October 1994 and February 1997. The calibration (closeness of total observed deaths to the predicted total) of models with published coefficients (SNAP-PE, CRIB, and NICHD) was assessed using the standardized mortality ratio. Discrimination was quantified as the area under the curve (AUC) for the receiver operating characteristic curves. Calibrated models were derived for the current database using logistic regression techniques. Goodness-of-fit of predicted to observed probabilities of death was assessed with the Hosmer-Lemeshow goodness-of-fit test. RESULTS: The calibration of published algorithms applied to our data was poor. The standardized mortality ratios for the NICHD, CRIB, and SNAP-PE models were.65,.56, and.82, respectively. Discrimination of all the models was excellent (range:.863-.930). Surprisingly, birth weight performed much better than in previous analyses, with an AUC of.869. The best models using both 12- and 24-hour postadmission data, significantly outperformed the best model based on birth data only but were not significantly different from each other. The variables in the best model were birth weight, birth weight squared, low 5-minute Apgar score, and SNAP (AUC =.930). CONCLUSION: Published models for severity of illness overpredicted hospital mortality in this set of VLBW infants, indicating a need for frequent recalibration. Discrimination for these severity of illness scores remains excellent. Birth variables should be reevaluated as a method to control for severity of illness in predicting mortality.

Female↗

Candida sepsis and association with retinopathy of prematurity.

OBJECTIVE: To assess the association of Candida sepsis with retinopathy of prematurity (ROP) in extremely low birth weight infants. METHODS: We prospectively identified 253 infants admitted to the Critical Care Nursery at Georgetown University Hospital with birth weights </=1000 g born between January 1, 1994, and June 30, 1996. Of these 253 infants, 62 died and 55 were transferred to other institutions before ophthalmologic screening for ROP. Clinical data on 98% (133/136) infants were reviewed. Candida sepsis was defined as a positive blood culture for Candida species. Severity of ROP was staged by the International Classification for ROP. Data were analyzed using the chi2 test for nominal data, unpaired t test for continuous data, Mann-Whitney U test for ordinal data, and logistic regression. RESULTS: The mean birth weight (+/-SD) of the population studied was 777 g (+/-136 g), and the mean gestational age at birth was 26.0 weeks (+/-1.8 weeks). The overall incidence of ROP was 74%, and it correlated significantly with birth weight, gestational age, days on supplemental oxygen, and 5-minute Apgar scores. The incidence of ROP was significantly higher in the infants who had Candida sepsis (21/22 [95%]) compared with those who did not (77/111 [69%]). Using logistic regression to control for the influence of birth weight, gestational age, days on supplemental oxygen, and 5-minute Apgar scores, Candida sepsis was an independent predictor of stage 3 or worse ROP. In addition, 9 (41%) of 22 infants with Candida sepsis required laser surgery compared with 10 (9%) of 111 infants without Candida sepsis. This difference was significant independent of birth weight, gestational age, days on supplemental oxygen, and 5-minute Apgar scores. CONCLUSIONS: Candida sepsis is independently associated with increased severity of ROP and the need for laser surgery in extremely low birth weight infants.

Candida↗

Human milk feedings and infection among very low birth weight infants.

BACKGROUND: Preterm infants are immunologically immature at birth. Previous studies have demonstrated that human milk protects against infection in full-term infants, but there are few studies of its effect for preterm infants. OBJECTIVE: To examine the effect of human milk feedings on infection incidence among very low birth weight (VLBW) infants during their initial hospitalization. STUDY DESIGN: The sample consisted of 212 consecutive VLBW infants admitted to the Georgetown University Medical Center neonatal intensive care unit (NICU) during 1992-1993 and surviving to receive enteral feeding. Type of feeding (human milk vs formula), presence of infection and sepsis/meningitis (clinical signs and positive cultures for pathogenic organisms), and potential confounding variables were abstracted from medical records. Multiple logistic regression was used to control for confounders. RESULTS: The incidence of infection (human milk [29.3%] vs formula [47.2%]) and sepsis/meningitis (human milk [19.5%] vs formula [32.6%]) differed significantly by type of feeding. Major risk factors for infection were similar in both groups. Human milk feeding was independently correlated with a reduced odds of infection (odds ratio [OR] = 0.43; 95% confidence interval [CI]: 0.23-0.81), controlling for gestational age, 5-minute Apgar score, mechanical ventilation days, and days without enteral feedings; and was independently correlated with a reduced odds of sepsis/meningitis (OR = 0.47, 95% CI:0.23-0. 95), controlling for gestational age, mechanical ventilation days, and days without enteral feedings. CONCLUSIONS: The incidence of any infection and sepsis/meningitis are significantly reduced in human milk-fed VLBW infants compared with exclusively formula-fed VLBW infants.

Apgar Score↗

Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants.

AIMS: To compare the effects of a single dose of frusemide administered either intravenously or by nebulisation on pulmonary mechanics in premature infants with evolving chronic lung disease. METHODS: The effect of frusemide on pulmonary mechanics was studied at a median postnatal age of 23 (range 14-52) days in 19 premature infants at 24 to 30 weeks gestational age, who had been dependent on mechanical ventilation since birth. Frusemide (1 mg/kg/body weight) was administered, in random order, intravenously and by nebulisation, on two separate occasions 24 hours apart. Pulmonary function studies were performed before and at 30, 60, and 120 minutes after administration of frusemide. Urine was collected for six hours immediately before and for six hours after administration of frusemide. RESULTS: Nebulised frusemide increased the tidal volume 31 (SE 11.5)% and compliance 34 (SE 12)% after two hours, whereas no change in either was noted for up to two hours after intravenous frusemide administration. Neither intravenous nor nebulised frusemide had any effect on airway resistance. Six hour urine output increased from a mean (SE) of 3.3 (0.4) ml/kg/hour to 5.9 (0.8) ml/kg/hour following intravenous frusemide administration while nebulised frusemide had no effect on urine output. Urinary sodium, potassium, and chloride losses were also significantly higher after intravenous frusemide, whereas nebulised frusemide did not increase urinary electrolyte losses. CONCLUSION: Single dose nebulised frusemide improves pulmonary function in premature infants with evolving chronic lung disease without adverse effects on fluid and electrolyte balance.

Administration, Inhalation↗

Health and neurodevelopmental outcome at 1-year adjusted age in 508 infants weighing 700 to 1100 grams who received prophylaxis with one versus three doses of synthetic surfactant. American Exosurf Neonatal Study Groups I and II.

A three-dose prophylactic regimen of synthetic surfactant replacement has been shown to improve neonatal and 1-year survival rates in infants of 700 to 1100 gm birth weight when compared with a single prophylactic dose. The purpose of this study was to evaluate the growth, development, and late morbidity at 1 year adjusted age among the survivors of the 826 patients enrolled in the protocol. Complete follow-up data were obtained for 75% of the survivors in both groups. Chronic lung disease, need for respiratory support, neurologic disease requiring medication, visual or auditory impairments, and the incidence and severity of retinopathy of prematurity were equivalent in the two groups. The frequency of neurodevelopmental impairment was also comparable in the groups that received one dose versus three doses: moderate to severe cerebral palsy was found in 9% versus 6%, mental retardation assessed by Bayley Scales of Infant Development scores less than 69 was found in 16% vs 14%, and moderate to severe impairments of any kind were found in 33% vs 24%, respectively. Furthermore, the absolute number of impaired survivors was 92 in the three-dose group versus 106 in the one-dose group, despite a higher survival rate in the three-dose group. This study demonstrates that developmental outcomes of infants weighing 700 to 1100 gm who received three prophylactic doses of synthetic surfactant are at least as good as those of infants receiving a single dose, and that improving survival rates of very premature infants with synthetic surfactant does not result in increased numbers of infants with impairments.

Child Development↗

Time of first stool in premature infants: effect of gestational age and illness severity.

OBJECTIVE: To assess the effect of gestational age and illness severity, and the effect of antenatal exposure to magnesium sulfate and glucocorticosteroids, on the timing of the first stool in preterm infants. METHODS: Medical records of all preterm infants (born at < or = 36 weeks of gestational age) admitted to the neonatal intensive care unit at Georgetown University Hospital between April 1993 and March 1994 were reviewed. We studied the time of the first stool in 221 infants after removing from the investigation the 45 infants who met the exclusion criteria. RESULTS: The median age of the infants at the time of the first stool was 18 hours, and 90% of the infants passed stool by 100 hours after birth. Both the gestational age and the illness severity, as measured by the Score for Neonatal Acute Physiology (SNAP), independently correlated with the timing of first stool (r = 0.31 and p < 0.0001 for gestational age; r = 0.33 and p < 0.0001 for SNAP). Of the 221 infants, 172 (78%) passed stool before the initiation of enteral feeding. Antenatal exposure to magnesium sulfate for tocolysis had no effect on the timing of the first stool, whereas infants whose mothers received glucocorticosteroids for enhancing fetal lung maturity passed their first stool significantly earlier than nonexposed infants of identical gestational age (p = 0.005). CONCLUSION: Delayed passage of first stool is a function of both illness severity and gestational immaturity. Antenatal betamethasone exposure leads to earlier stool passage, whereas antenatal exposure to magnesium sulfate does not affect the timing of first stool in premature infants.

Adrenal Cortex Hormones↗

Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung.

Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with potent phospholipase A2-inhibitory activity. It has been suggested that during implantation this protein protects the embryos from maternal immunological assault, facilitates the maintenance of quiescence in the uterus throughout pregnancy, prevents the onset of premature labor, and helps maintain an inflammation-free respiratory organ. This latter function of UG is suggested to be accomplished by preventing hydrolysis of surfactant phospholipids by a lung-specific phospholipase A2. Using reverse transcription polymerase chain reaction, in situ hybridization, immunofluorescence, and radioimmunoassay, we studied UG gene expression in the rabbit uterus throughout gestation and in the fetal lung. Here, we report that: (a) contrary to previous reports, UG gene expression in the rabbit uterus occurs throughout gestation with a precipitous decline just before parturition; (b) this gene expression is dramatically increased in the fetal lung with increasing gestational age; and (c) while there is an inverse relationship between the levels of UG, PGE2, and PGF2 alpha, a positive correlation was found in that of UG and leukotriene C4 in the fetal lung. Our results raise the possibility that dysregulation of UG gene expression, at least in part, may contribute to the onset of premature labor and the development of inflammatory lung disease in premature neonates.

Animals↗

Effect of intrauterine cocaine exposure on respiratory distress syndrome in very low birthweight infants.

To evaluate the effect of intrauterine cocaine exposure on lung maturity of very low birthweight infants, the medical records of all infants with birthweight < 1500 g born between January 1989 and December 1990 at DC General Hospital were reviewed. Infants with conditions known to cause lung maturity, severe congenital anomalies, proven early sepsis, and birthweight > or = 500 g were excluded. A total of 69 infants were included in the study. Chest roentgenograms of these infants were evaluated by a pediatric radiologist, who was unaware of the infant's medical course, for evidence of respiratory distress syndrome (RDS), and radiological findings were correlated with clinical signs. Forty infants were exposed to cocaine in utero (cocaine group) and 29 were not exposed (noncocaine group). African-American ethnicity, pregnancy-induced hypertension, prolonged rupture of membranes, and alcohol use were similar in both groups. Tobacco use among cocaine group mothers was higher (42.5% versus 13.8%; P = .01). Gestational age (28.3 +/- 2.8 versus 28.3 +/- 3 weeks), birthweight (966 +/- 282 versus 1059 +/- 295 g), male gender, and Apgar scores were similar in both groups. Thirty (75%) infants in the cocaine group developed RDS compared with 19 (66%) in the noncocaine group (P > .05). Using multiple logistic regression analysis and controlling for smoking, alcohol use, and prolonged rupture of membranes (24 to 72 hours), the incidence of RDS between the groups remained statistically insignificant. We conclude that intrauterine cocaine exposure does not alter the incidence of RDS in very low birthweight infants.

Cocaine↗

Time of first stool in extremely low birth weight (< or = 1000 grams) infants.

The time of first stool was studied in 144 infants with a birth weight of 1000 gm or less. Median age at passage of the first stool was 3 days, and 90% of the infants passed stool by 12 days after birth. There was no relationship between the time of passage of the first stool and either birth weight or gestational age. Of the 114 infants, 88 (77%) passed stool before the initiation of any enteral feeding. The passage of the first stool was delayed in male compared with female infants (p = 0.03).

Birth Weight↗

Urine collection from disposable diapers in premature infants: biochemical analysis.

Urine collection for analysis is commonly done in premature infants in sterile adhesive bags. Leakage due to poor adherence of the bag and irritation of the skin are frequent drawbacks with this technique. Urine retrieved from the fiber padding of disposable diapers has been shown to be reliable for biochemical analysis. However, the previous studies were done under laboratory conditions and the volume of urine used was much larger than a premature infant may void at one time. The purpose of this study was to determine the reliability of urine collected from disposable diapers for biochemical analysis in premature infants in the intensive care nursery.

Disposable Equipment↗

Surfactant-producing rabbit pulmonary alveolar type II cells synthesize and secrete an antiinflammatory protein, uteroglobin.

Neonatal respiratory distress syndrome (RDS) caused by surfactant deficiency is a common disorder in premature infants. Exogenous surfactant therapy improves survival in infants with RDS. However, the phospholipid component of the surfactant has been suggested to be inactivated by a phospholipid hydrolyzing enzyme, phospholipase A2 (PLA2). Although alveolar type II cells produce the surfactant, it is not known whether these cells have any mechanism to protect surfactant from PLA2 hydrolysis. Since alveolar Clara cells express uteroglobin (UG), a PLA2 inhibitory and antiinflammatory protein, and since it has been suggested that alveolar type II cells are derived from Clara cells, we sought to elucidate whether type II cells are also capable of expressing UG gene. By using radioimmunoassay, immunoprecipitation and Western blotting techniques we demonstrate for the first time that type II cells, isolated from mature rabbit lungs, synthesize and secrete UG. The transcription of the UG gene was detected by in situ hybridization using rabbit UG cDNA probe. These results imply that UG, synthesized by type II cells, may protect both endogenous and exogenous surfactant from PLA2 hydrolysis. Moreover, the antiinflammatory properties of UG may prevent the development of chronic inflammatory lung disease, a frequent complication of RDS.

Animals↗

Effects of saline instillation during tracheal suction on lung mechanics in newborn infants.

To evaluate the effect of saline instillation prior to tracheal suction on lung mechanics in mechanically ventilated newborn infants, we studied pulmonary mechanics in nine infants with respiratory distress syndrome (RDS) and nine infants with meconium-aspiration syndrome (MAS) at a mean postnatal age of 3 days. Pulmonary mechanics were measured at 10 minutes prior to, and at 10, 20, and 30 minutes after tracheal suction with saline instillation. Suction and study protocol were repeated within 12 hours without saline instillation. The sequence of the study with and without saline instillation was randomly assigned. In infants with RDS, tracheal suction had no effect on pulmonary compliance or airway resistance with and without saline instillation. In infants with MAS, there was no change in compliance after tracheal suction with and without saline instillation. Airway resistance decreased by 35% after tracheal suction with saline instillation in infants with MAS; tracheal suction without saline instillation had no effect on airway resistance. We conclude that saline instillation into trachea as commonly done during tracheal suction has no deleterious effects on lung mechanics in newborn infants.

Airway Resistance↗