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Biomedical subjects

R deLemos

Publications and source records attributed to R deLemos.

9 recordsLinked to original sources

A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates.

OBJECTIVE: We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs. STUDY DESIGN: VLBWNs (n = 264), weighing 501 to 1000 g, </=72 hours of age were randomly assigned to receive rhu GM-CSF (8 microg/kg/d), administered intravenously (n = 134) over 2 hours daily x 7 days and every other day for 21 days, or placebo (n = 130). The safety, incidence of nosocomial infections, days of absolute neutrophil count >/=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups. RESULTS: No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS). CONCLUSION: In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.

Cross Infection↗

Structure of the human Nkx2.1 gene.

NKX2.1 is a member of the NK2 family of homeodomain-containing transcriptional factors which binds to and activates the promoters of thyroid and pulmonary epithelial genes. We have cloned and sequenced twelve human lung NKx2.1 cDNAs. To elucidate the origin of Nkx2.1 transcripts, we also cloned and sequenced a 12 kb human Nkx2.1 genomic clone. Alignment of cDNA sequences with the genomic clone showed that contrary to previous reports, the human Nkx2.1 gene is organized into three exons and two introns. The newly discovered exon I contains an ATG codon that falls in frame with the previously identified Nkx2.1 initiator ATG codon on one of the cDNAs, designated 5E. Northern blot analysis shows that an mRNA of approximately 2.5 kb in size, homologous to 5E, is expressed in both lung and thyroid. The deduced amino acid sequence of the longest open reading frame on 5E is identical to NKX2.1 with the exception of a 30 amino acid N-terminal extension. Coupled in vitro transcription/translation of the 5E cDNA confirms that the open reading frame is translated into a contiguous polypeptide of 44 kDa. Analysis of Nkx2.1 genomic DNA fragments suggest that at least two independent regions, one within the first intron and the other 5' of the first exon may mediate the basal promoter activity of the Nkx2.1 gene in lung epithelial cells.

Amino Acid Sequence↗

Comparison of dynamic and passive measurements of respiratory mechanics in ventilated newborn infants.

Pulmonary mechanics may differ in intubated and ventilated infants depending on whether they are measured by a dynamic or passive method. The objective of this study was to compare respiratory mechanics measured by a dynamic technique with those obtained by a single-breath occlusion technique in ventilated newborn infants. Thirty-one preterm and 15 term infants (mean +/- SD: gestational age, 29.3 +/- 2.3 and 39.5 +/- 1.4 weeks; birth weight, 1.2 +/- 0.5 and 3.4 +/- 0.4 kg; postnatal age, 12 +/- 13 and 5 +/- 4 days, respectively) were studied. Flows were measured through a pneumotachometer placed between the endotracheal tube and the ventilator circuit: tidal volume by integration of flow, and airway pressure directly with a pressure transducer. Airway occlusion was performed with a Neonatal Occlusion Valve (Bicore pulmonary monitor) at the end of inspiration, and the following relaxed exhalation was analyzed to give passive respiratory system compliance (Crs) and resistance (Rrs). These values were compared with dynamic respiratory system compliance (Cdyn) and dynamic expiratory resistance (Re) obtained with the PEDS system (P) within 1 hour, without an esophageal balloon and on the same ventilator settings. Dynamic respiratory system compliance and resistance measured with the PEDS and the Bicore systems did not differ significantly and were well correlated. Mean Cdyn (P) values in preterm and term infants were 77% and 77% of Crs; the equation of the regression line was Cdyn = 0.75 Crs + 0.02 and Cdyn = 0.78 Crs - 0.02; and standard error of the estimate (SEE) was 0.2 and 0.3 mL/cmH2O with a correlation coefficient (r) of 0.89 and 0.89 (P < 0.0001), respectively. The mean Re(P) values in preterm and term infants were 68% and 64% of Rrs, and the equation of the regression line was Re = 0.3 Rrs + 63 and Re = 0.5 Rrs + 20, with SEE of 25 and 20 cmH2O/L/sec, and r of 0.65 and 0.69 (P < 0.0001, P < 0.005), respectively. The two methods are non-invasive and were well tolerated. We conclude that passive and dynamic respiratory compliance and resistance measured in intubated infants are highly correlated, although the values measured by the passive technique are higher than those obtained by the dynamic technique.

Airway Resistance↗

TTF-1 regulates lung epithelial morphogenesis.

TTF-1 is a homeodomain transcriptional factor expressed in thyroid, lung, and parts of the brain. In vitro, TTF-1 can activate the promoter of thyroid- and pulmonary-specific genes. We postulated that TTF-1 not only is essential for the activation of tissue-specific genes, but also may directly participate in epithelial cell morphogenesis. To test this postulate, we used an antisense oligonucleotide inhibitory strategy in an in vitro model of embryonic mouse lung branching morphogenesis. This strategy suppressed TTF-1 translation and inhibited lung branching morphogenesis. The resulting abnormal phenotype was characterized by hyperplastic and unorganized proliferation of epithelial cells in the airways. The mesenchymal compartment of the lung appeared to be unaffected. These results demonstrate, for the first time, that the expression of a homeoprotein transcriptional regulator is necessary for lung epithelial morphogenesis.

Animals↗

Pulmonary interstitial emphysema in the premature baboon with hyaline membrane disease.

During experiments designed to develop an appropriate ventilatory strategy for high-frequency ventilation (HFV) in the premature baboon with hyaline membrane disease (HMD), we observed the development of pulmonary interstitial emphysema (PIE). Four study groups of 5 animals each received positive-pressure ventilation and positive end-expiratory pressure (PPV/PEEP) or HFV and 1 of 3 sighing techniques. Pathologically, all animals ventilated with PPV/PEEP or HFV with a carefully controlled intermittent sigh developed dilatation of the distal conducting airway and alveolar duct, with poorly expanded pulmonary saccules. The imposition of a sigh with inappropriate timing or excessive volume ruptured the dilated airway walls and caused interstitial air to accumulate. This was evident from the location of striking dilation of the distal airways and pseudocysts in areas of atelectasis. Thus, early in the course of HMD when saccular aeration is minimal, the pathogenesis of PIE is related to airway rather than alveolar rupture.

Animals↗

The use of high-frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation (ECMO) in the management of the term/near term infant with respiratory failure.

The use of high-frequency oscillatory ventilation (HFOV) was evaluated as a rescue intervention in 122 consecutive infants meeting criteria for extracorporeal membrane oxygenation (ECMO). Fifty-three percent responded to HFOV and never required ECMO, 3/65 died. Infants who ultimately required ECMO had lower aortic and pulmonary peak flow velocities, and lower pulmonary acceleration, circumferential fiber shortening and shortening fraction than those who were successfully managed with HFOV. The use of HFOV with an appropriate strategy decreased the need for ECMO in this patient population.

Extracorporeal Membrane Oxygenation↗

Very low birth weight infants and their families during the first year of life: comparisons of psychosocial outcomes based on after-care services.

OBJECTIVE: To evaluate psychosocial outcomes in families of very low birth weight infants during the first year postdischarge. STUDY DESIGN: This was a prospective investigation of family functioning in families of 81 very low birth weight infants discharged from two tertiary care neonatal intensive care units in Los Angeles, CA. Infants were assigned to four groups receiving a variety of after-care services in their homes. Analyses of variance and t-tests were used to examine differences in outcomes, including parental involvement with infant, maternal depression, and family adaptation and cohesion over time. RESULTS: During the first year following discharge, there were no differences between after-care groups in levels of maternal depression as measured by the Center for Epidemiologic Studies Depression Scale or family cohesion and adaptability as measured by the Family Adaptability and Cohesion Evaluation Scales II. Significant between-group differences were seen on measures of home environment at both 6 and 12 months and self-reports of satisfaction with parenting at 6 months. CONCLUSION: Results of this study indicate that types of after-care services do not change basic maternal or family characteristics. However, long-term home-visiting services appear to impact the way mothers interact with their high-risk infants. Furthermore, such services seem to influence a mother's perception of satisfaction with her role.

Adult↗

Very low birth weight infants and their families during the first year of life: comparisons of medical outcomes based on after care services.

OBJECTIVE: To evaluate factors contributing to optimal medical outcomes during the first year following discharge of very low birth weight infants from tertiary neonatal intensive care units. STUDY DESIGN: This was a prospective investigation of the health and development of 81 very low birth weight infants following discharge from two tertiary neonatal intensive care units in Los Angeles. Infants were assigned to four groups receiving a variety of after care services in their homes. Analyses of variance were computed to examine differences between groups for a variety of outcomes. RESULTS: No statistically significant differences were seen between after care groups on use of hospital emergency rooms (ER) rehospitalization rates, or child abuse and neglect. Highest overall rates of optimal outcomes were seen in the group receiving the highest intensity of after care services. Those groups receiving long-term home visiting services had significantly higher rates of up-to-date immunizations. CONCLUSION: There was no significant impact on infant mortality and morbidity of early discharge, regardless of the system of after care used. However, those infants who received the highest level of after care services had the most optimal health outcomes and were most likely to be receiving well-baby care. It is likely that the comprehensive, clinic-based system of health care available to all study infants was a significant factor in low rates of morbidity.

Aftercare↗