Biomedical subjects

S J Chen

Publications and source records attributed to S J Chen.

At least 19 recordsLinked to original sources

PubMed1999

Chromosomal aberrations during progression of chronic myeloid leukemia identified by cytogenetic and molecular cytogenetic tools: implication of 1q12-21.

To study the genomic abnormality underlying the acute transformation of chronic myeloid leukemia (CML), 15 CML patients in blast crisis (BC), 3 in accelerated phase (AP), and 20 in chronic phase (CP) were analyzed by conventional cytogenetics, comparative genomic hybridization (CGH), and dual-color chromosomal painting. Philadelphia (Ph) chromosome was identified in every case studied. Only 5 among 20 CP patients had additional abnormalities while 13 of 18 patients with disease progression (BC + AP) showed extra numerical and/or structural chromosomal aberrations. Cytogenetically, the most common chromosome gains during BC and AP were double or triple Ph chromosomes (5 of 14 cases) and trisomy 8 (5 of 14 cases). Trisomies 7 and 17 (1 of 14 cases each) were also observed. CGH analysis detected genetic imbalances in eight cases. Gains of chromosome 20 (3 cases) and 17q (2 cases) were observed, respectively. The recurrent chromosome loss was the deletion of the short arm of chromosome 17, seen in one case with i(17)(q10) and one case with an unbalanced translocation (1;17). In one case, a very complex chromosomal rearrangement, del(3),del(6),der(6)t(17;3;6),der(17)t(6;17), was seen. A novel finding of this work is the involvement of chromosome 1(q12-21qter) in CML disease progression. Overrepresentation of 1(q12-21qter) region was detected by CGH in one case which had a derivative chromosome 17. This abnormal chromosome was later confirmed by fluorescence in situ hybridization (FISH) painting to be a fusion between chromosome 1 and 17 to form the der(17)t(1;17) (q12-21;p11). Two other cases showed the same region being involved in translocations, t(1;10)(q12-21;q26) and t(1;11)(q12-21;p15). It is possible that one or more genes residing on chromosome 1q12-21 may be important in the acute transformation of CML. In conclusion, we find that the combined use of CGH, chromosome painting, and classic cytogenetic analysis allows a better evaluation of the genomic aberration involved in CML blastic transformation, and offers new directions for its further molecular investigations.

Adult↗

PubMed1999

Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3.

Transforming growth factor-beta (TGF-beta) stimulates the transcription of the alpha2(I) procollagen gene (COL1A2). The intracellular mediators involved in this response remain poorly understood. In this study, we demonstrate that primary human skin fibroblasts express Smads, a novel family of signaling molecules, in vitro in the absence of TGF-beta. The levels of Smad 7 mRNA was rapidly and transiently increased by TGF-beta. Transient overexpression of Smad 3 and Smad 4, but not Smad 1 or Smad 2, caused trans-activation of a CAT reporter gene driven by a 772 bp segment of the human COL1A2 promoter containing putative TGF-beta response elements. Smad stimulation of promoter activity was ligand independent, but was further enhanced by TGF-beta. Overexpression of a phosphorylation-deficient Smad 3 mutant or wild-type Smad 7, which lacks the carboxy-terminal phosphorylation motif, specifically inhibited TGF-beta-induced activation of COL1A2 promoter. A CAGACA sequence shown to be a functional Smad-binding element in the plasminogen activator inhibitor-1 gene promoter was found within the TGF-beta-response region of the proximal COL1A2 promoter. Gel mobility shift assays showed protein phosphorylation-dependent binding activity in fibroblast nuclear extracts specific for this sequence; TGF-beta treatment strongly stimulated the formation of this DNA-protein complex. Smad was identified as a component of the CAGACA-binding transcription complex in TGF-beta-treated fibroblasts by antibody supershifting. These results demonstrate that (i) Smad 3 transmits TGF-beta signals from the receptor to the COL1A2 promoter in human fibroblasts, and is likely to play an important role in stimulation of COL1A2 promoter activity elicited by TGF-beta; (ii) in fibroblasts, Smads appear to function as inducible DNA-binding transcription factors; and (iii) Smad 7 may be involved in autocrine negative feedback in the regulation of COL1A2 promoter activity by TGF-beta.

Cells, Cultured↗

PubMed1998

Modulation of human alpha1(I) procollagen gene activity by interaction with Sp1 and Sp3 transcription factors in vitro.

In previous work, we delineated a proximal region of the human alpha1(I) collagen gene (COL1A1) promoter necessary to direct its basal transcription in fibroblasts. This region has potential recognition sites for a variety of DNA-binding proteins. Here, we show that the -129/-107-bp sequence in this region of the promoter, which harbors an inverted CCAAT motif closely linked to a GC-rich direct repeat and is perfectly conserved between mouse and human, specifically bound the transcription factors Sp1, Sp3, and CTF/NF-1 in nuclear extracts from human skin and lung fibroblasts. Drosophila Schneider L2 cells lacking endogenous Sp activity were used to investigate the effect of expression of Sp or CTF/NF-1 transcription factors on COLlAl promoter activity. Expression of Sp1 caused potent trans-activation of a COL1A1 promoter (-174 to +42bp). In contrast, expression of Sp3, which binds to the same recognition sites as Sp1, and CTF/NF-1 stimulated COL1A1 promoter activity only at higher concentrations, and Sp2 did not transactivate. Expression of a 10-fold excess of Sp3, but not CTF/NF-1 or Sp2, abrogated the stimulation of COL1A1 promoter activity induced by Sp1. TGF-beta at concentrations previously shown to increase COL1A1 transcription caused a decrease in the relative amount of Sp3 in fibroblast nuclear extracts. These results suggest that both Sp1 and Sp3 bind to the proximal COL1A1 promoter and stimulate its activity; however, their interaction with each other may result in repression of Sp1-induced COL1A1 transcription. Alterations in the relative amounts or DNA-binding activities of these transcription factors in a cell- or signal-specific manner may contribute to the control of transcription from the COL1A1 promoter. The present findings, and recent observations implicating Sp1 and its homologs in regulating the expression of several collagen genes, suggest that the family of Sp1 transcription factors play a role in physiological and pathological modulation of connective tissue accumulation.

Animals↗

PubMed1998

Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.

Hematopoietic stem/progenitor cells (HSPCs) possess the potentials of self-renewal, proliferation, and differentiation toward different lineages of blood cells. These cells not only play a primordial role in hematopoietic development but also have important clinical application. Characterization of the gene expression profile in CD34(+) HSPCs may lead to a better understanding of the regulation of normal and pathological hematopoiesis. In the present work, genes expressed in human umbilical cord blood CD34(+) cells were catalogued by partially sequencing a large amount of cDNA clones [or expressed sequence tags (ESTs)] and analyzing these sequences with the tools of bioinformatics. Among 9,866 ESTs thus obtained, 4,697 (47.6%) showed identity to known genes in the GenBank database, 2, 603 (26.4%) matched to the ESTs previously deposited in a public domain database, 1,415 (14.3%) were previously undescribed ESTs, and the remaining 1,151 (11.7%) were mitochondrial DNA, ribosomal RNA, or repetitive (Alu or L1) sequences. Integration of ESTs of known genes generated a profile including 855 genes that could be divided into different categories according to their functions. Some (8.2%) of the genes in this profile were considered related to early hematopoiesis. The possible function of ESTs corresponding to so far unknown genes were approached by means of homology and functional motif searches. Moreover, attempts were made to generate libraries enriched for full-length cDNAs, to better explore the genes in HSPCs. Nearly 60% of the cDNA clones of mRNA under 2 kb in our libraries had 5' ends upstream of the first ATG codon of the ORF. With this satisfactory result, we have developed an efficient working system that allowed fast sequencing of 32 full-length cDNAs, 16 of them being mapped to the chromosomes with radiation hybrid panels. This work may lay a basis for the further research on the molecular network of hematopoietic regulation.

ATPases Associated with Diverse Cellular Activitie↗

PubMed1998

Identification of active site residues in Escherichia coli DNA topoisomerase I.

Alanine substitution mutagenesis of Escherichia coli DNA topoisomerase I, a member of the type IA subfamily of DNA topoisomerases, was carried out to identify amino acid side chains that are involved in transesterification between DNA and the active site tyrosine Tyr-319 of the enzyme. Twelve polar residues that are highly conserved among the type IA enzymes, Glu-9, His-33, Asp-111, Glu-115, Gln-309, Glu-313, Thr-318, Arg-321, Thr-322, Asp-323, His-365, and Thr-496, were selected for alanine substitution. Each of the mutant enzymes was overexpressed, purified, and characterized. Surprisingly, only substitution at Glu-9 and Arg-321 was found to reduce the DNA relaxation activity of the enzyme to an insignificant level. The R321A mutant enzyme, but not the E9A mutant enzyme, was found to retain a reduced level of DNA cleavage activity. Two additional mutant enzymes R321K and E9Q were also constructed and purified. Replacing Arg-321 by lysine has little effect on enzymatic activities; replacing Glu-9 by glutamine greatly reduces the supercoil removal activity but not the DNA cleavage and rejoining activities. From these results and the locations of the amino acids in the crystal structure of the enzyme, it appears that Glu-9 has a critical role in DNA breakage and rejoining, probably through its interaction with the 3' deoxyribosyl oxygen. The positively charged Arg-321 may also participate in these reactions by interacting with the scissile DNA phosphate as a monodentate. Because of the strict conservation of these residues, the findings for the E. coli enzyme are likely to apply to all type IA DNA topoisomerases.

Amino Acid Sequence↗

PubMed1998

Usefulness of electron beam computed tomography in children with heterotaxy syndrome.

Children with heterotaxy syndrome frequently have complex cardiac and noncardiac malformations requiring detailed diagnostic evaluation for management planning. Direct delineation of these structures by electron beam computed tomography (EBCT) is validated as a means of diagnosis. From July 1995 to March 1997, 32 patients (16 girls, 16 boys) with clinically impressed heterotaxy syndrome were enrolled in this study. After evaluation by echocardiography, EBCT studies were performed. Interpretation of cardiac anomalies was performed by sequential analysis based on these cross-sectional images. The diagnoses were subsequently confirmed by angiocardiography and surgical findings. Twenty-eight patients had bilateral trifurcated bronchi, and most of these (24 of 28) did not have a spleen. Four patients had bilateral bifurcated bronchi, 2 patients had polysplenia, and the other 2 patients had a lobulated single spleen. We found that laterality could be identified by EBCT in all patients. Comparison of diagnostic yield between echocardiography, catheterization, and EBCT showed that EBCT is superior to echocardiography and catheterization in demonstration of pulmonary venous anatomy and presence of a very small rudimentary ventricle. In addition, associated visceral, bronchopulmonary, mediastinal, and intracardiac anomalies could all be clearly delineated by EBCT at the same time. Thus, EBCT is a promising complementary modality for an overall understanding of heterotaxy syndrome.

Abnormalities, Multiple↗

PubMed1998

Is the short insulin tolerance test safe and reproducible?

The short insulin tolerance test (SITT) is described as a simple method to measure insulin sensitivity. To investigate the safety and reproducibility of the SITT, 16 healthy volunteers underwent two SITTs within 1 week. Intravenous insulin (0.05 U kg(-1) body weight) was injected into an antecubital vein. Blood samples were collected from the contralateral antecubital vein. The insulin-induced glucose disposal rate (Kitt) was calculated from the slope of the regression line of the logarithm of blood glucose against time during the first 3-15 min. Plasma glucose concentrations fell below 2.8 mmol l(-1) in 4 of the 32 tests and below 2.2 mmol I(-1) in 1 of these 4. Five subjects had mild hypoglycaemic symptoms, three of whom had plasma glucose concentrations below 2.8 mmol l(-1) in at least one SITT. The mean Kitt was 4.2% min(-1) (range 0.8-8.4) for the first test and 3.4% min(-1) (range 0.1-6.8) for the second test. The mean within-subject coefficient of variation was 30.7%. We conclude that SITT should be applied with caution especially on insulin sensitive subjects and has poor reproducibility using 0.05 U kg(-1) body weight of insulin injection, venous sampling, uncontrolled physical activity and uncontrolled dietary composition. Whether 0.1 U kg(-1) body weight of insulin injection and arterialized venous blood sampling as in the original description of this test can improve the reproducibility of the SITT needs further investigation.

Adult↗

PubMed1998

Endogenous Candida endophthalmitis after induced abortion.

PURPOSE: To report two young healthy women who developed endogenous Candida endophthalmitis after undergoing surgically induced abortion. METHOD: Case reports. RESULTS: In two eyes of two patients, a diagnosis of Candida endophthalmitis was established by typical fundus appearance, positive vaginal culture, and, in one case, positive vitreous culture. After vitrectomy and intravitreal amphotericin B injection, one eye of one patient had a best-corrected visual acuity of 20/200, whereas one eye of one patient, who had systemic corticosteroid treatment before the correct diagnosis, developed recurrent retinal detachment and a best-corrected visual acuity of counting fingers. CONCLUSIONS: Induced abortion may cause endogenous Candida endophthalmitis in young healthy pregnant women. Systemic corticosteroid treatment may increase the risk of endophthalmitis.

Abortion, Induced↗

PubMed1998

Effect of the gasoline additives on PAH emission.

PAH emission from the powered engines fueled by a 95 leadfree gasoline (95-LFG), a 92 leadfree gasoline (92-LFG) and a Premium leaded gasoline (PLG) with two gasoline additives (SA and SB) were collected using a PAH sampling system with a particulate interception device. Twenty one PAHs were analyzed primarily by an GC/MS, while eight metal elements were determined mainly by an ICP-AES. This investigation showed that the gasoline additives contain more amounts of carcinogenic PAHs than gasolines do. Blending these additives do raise the PAH content in the gasolines, simultaneously, will emit more amount of PAHs from the tailpipe of engine exhaust. It is suggested that before a gasoline additive is commercialized, an assessment on its PAH emission should be evaluated to make sure that the additive will not emit more PAHs and cause adverse effect on public health.

Carcinogens↗

PubMed1998

Detection of chromosome over- and underrepresentations in hyperdiploid acute lymphoblastic leukemia by comparative genomic hybridization.

Chromosomal analysis of acute lymphoblastic leukemia (ALL) is often difficult because of the suboptimal in vitro growth of the immature lymphoid cell and the poor morphology obtained. In this study, we describe the application of comparative genomic hybridization (CGH) to investigate the genomic abnormalities in 14 patients with ALL, all of whom had cytogenetically identified numerical aberrations or gross chromosomal structural alteration. With the use of CGH, regional or whole chromosome overrepresentation or both were found to be more frequent than underrepresentation (52 gains vs. 6 losses), the most common gains being chromosomes 21 and X. The results of the comparison between CGH and conventional R-banding analysis could be classified into three categories: (1) in three cases, including two with trisomy, CGH and banding analysis gave identical results; (2) in six cases with hyperdiploidy and two cases presenting chromosome structural abnormalities, the results were consistent but with minor discrepancies; (3) in three cases, including two with triploidy and tetraploidy and one with chimeric karyotype together with +22, the data from CGH and cytogenetical analysis were discrepant. CGH could not find the triploidy and tetraploidy. Our results suggest that CGH has certain value in the detection of gains or losses of chromosome materials in hyperdiploid ALL. Nevertheless, the combination of CGH and conventional karyotyping provides more precise information on the genomic imbalance in ALL.

Adolescent↗

PubMed1998

Modulation of basal expression of the human alpha1(I) procollagen gene (COL1A1) by tandem NF-1/Sp1 promoter elements in normal human dermal fibroblasts.

We previously demonstrated that a segment of the human alpha1 type I procollagen gene (COL1A1) promoter encompassing nt -174 to -84 is responsible for the highest transcriptional activity in collagen producing cells in vitro. Here, we identified two almost identical tandem NF-1/Sp1 binding sites located between nt -129 to -107 (distal element) and nt -104 to -77 (proximal element) that are responsible for the basal regulation of COL1A1 transcription in normal human dermal fibroblasts. Transient transfection studies revealed that 85% of the basal COL1A1 promoter activity resides within the distal element; however, site-directed mutagenesis within the CCAAT motif in the proximal element resulted in a 98% decrease of the COL1A1 promoter activity. We conclude that each of the NF-1/Sp1 tandem binding sites has a different function. The distal element drives the transcriptional activity of the COL1A1 promoter but is not sufficient for its basal expression, whereas the NF-1 binding site in the proximal element is essential for in vitro COL1A1 gene transcription.

Base Sequence↗

PubMed1998

Chemical hypoxia triggers apoptosis of cultured neonatal rat cardiac myocytes: modulation by calcium-regulated proteases and protein kinases.

Myocardial infarctions and stroke arise primarily as a result of hypoxia/ischemia-induced cell injury. However, the molecular mechanism of cardiac cell death due to hypoxia has not been elucidated. We showed here that chemical hypoxia induced by 1 mM azide triggered apoptosis of isolated neonatal rat ventricular cardiac myocytes but had no effect on cardiac fibroblasts. The azide-induced cardiomyocyte apoptosis could be characterized by a reversible initiation phase (0-46 h after azide exposure) during which cytosolic ATP levels remained little affected. This was followed by an irreversible execution phase (12-18 h) exhibiting prominent internucleosomal DNA fragmentation, cell membrane leakage, mitochondrial dysfunction, and increased calpain messenger RNA. Blocking extracellular calcium influx or intracellular calcium release was each effective in suppressing myocyte apoptosis. Cell death was also found to be mediated by calcium sensitive signal transduction events based on the use of specific antagonists. Consistent with the induction of calpain expression during apoptosis, blocking de novo protein synthesis and calpain activity inhibited cell death. These regulatory features coupled with the ease of the cell system suggest that the myocyte apoptosis model described here should be useful in the study of events leading to the demise of the myocardium.

Animals↗

PubMed1998

Protected-site phosphorylation of protein kinase C in hippocampal long-term potentiation.

One important aspect of synaptic plasticity is that transient stimulation of neuronal cell surface receptors can lead to long-lasting biochemical and physiological effects in neurons. In long-term potentiation (LTP), generation of autonomously active protein kinase C (PKC) is one biochemical effect persisting beyond the NMDA receptor activation that triggers plasticity. We previously observed that the expression of early LTP is associated with a phosphatase-reversible alteration in PKC immunoreactivity, suggesting that autophosphorylation of PKC might be elevated in LTP. In the present studies we tested the hypothesis that PKC phosphorylation is persistently increased in the early maintenance of LTP. We generated an antiserum that selectively recognizes the alpha and betaII isoforms of PKC autophosphorylated in the C-terminal domain. Using western blotting with this antiserum we observed an NMDA receptor-mediated increase in phosphorylation of PKC 1 h after LTP was induced. How is the increased phosphorylation maintained in the cell in the face of ongoing phosphatase activity? We observed that dephosphorylation of PKC in vitro requires the presence of cofactors normally serving to activate PKC, i.e., Ca2+, phosphatidylserine, and diacylglycerol. Based on these observations and computer modeling of the three-dimensional structure of the PKC catalytic core, we propose a "protected site" model of PKC autophosphorylation, whereby the conformation of PKC regulates accessibility of the phosphates to phosphatase. Although we have proposed the protected site model based on our studies of PKC phosphorylation in LTP, phosphorylation of protected sites might be a general biochemical mechanism for the generation of stable, long-lasting physiologic changes.

Amino Acid Sequence↗

PubMed1998

Coxsackievirus B1 infection in infants less than 2 months of age.

Most of the neonatal enteroviral infections reported in the literature are associated with Coxsackievirus B2-B5 and echovirus 9 and 11. We report a retrospective Coxsackievirus B1 (CB1) infection in infants less than 2 months of age. Seventeen patients had aseptic meningitis and 8 had systemic sepsis (multi-organ involvement including meningitis, impaired liver function, and abnormality in coagulation). The symptoms and signs were nonspecific and could not be distinguished with bacterial infection on clinical grounds. Virus isolation was mandatory for diagnosis. Impaired liver function and coagulation profiles were noted in patients with systemic sepsis, but not in patients with meningitis only. CSF examination showed some uncommon features of viral meningitis: predominance of polymorphonuclear cells (PMN) was noted in 62.5% of patients and hypoglycorrhachia in 64% of patients. The patients with only meningitis recovered completely without any sequela. One of the eight patients with systemic sepsis died with case fatality rate 12.5%. Physicians should be aware of the possibility of CB1 virus infection in young infants during prevalent seasons. Specimens should be sent for viral culture in patients with meningitis and sepsis to make a definite diagnosis.

Age of Onset↗

PubMed1998

Nitric oxide-independent activation of soluble guanylyl cyclase contributes to endotoxin shock in rats.

We investigated whether a complete inhibition of nitric oxide (NO) formation caused by bacterial endotoxin (lipopolysaccharide, LPS) in vivo prevents the hypotension and restores the vascular hyporeactivity to normal in vivo and ex vivo. The combination of dexamethasone (Dex; 3 mg/kg at 30 min before LPS) plus aminoguanidine (AG; 15 mg/kg at 2 h after LPS) inhibited the overproduction of nitrate (an indicator of NO) in the plasma and aortic smooth muscle and also prevented the development of the delayed hypotension in rats treated with LPS for 6 h. However, the vascular hyporeactivity to norepinephrine (NE) was only partially improved either in vivo or ex vivo in endotoxemic rats treated with Dex plus AG. Pretreatment of aortic rings with Nomega-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2, 4]oxidazolo[4,3-a]quinoxalin-1-one (ODQ) enhanced the contraction to NE in rings obtained from LPS-treated rats, but not in those from Dex plus AG-treated endotoxemic rats. Methylene blue, an inhibitor of soluble guanylyl cyclase (GC), completely restored contractions to NE and aortic cGMP levels to normal either in LPS-treated rats or in Dex plus AG-treated endotoxemic rats, whereas the cGMP level was partially inhibited by ODQ in LPS-treated rats only. These results suggest that non-NO mediator(s) also activates soluble GC during endotoxemia. Interestingly, we found that in the presence of tetraethylammonium (an inhibitor of K+ channels) plus L-NAME or charybdotoxin [a specific inhibitor of large-conductance Ca2+-activated K+ (KCa) channels] plus ODQ, the vascular hyporeactivity to NE in the LPS-treated group was also completely restored to normal. In addition, in the presence of L-NAME or ODQ, the vascular hyporeactivity to high K+ was abolished in rings from the LPS-treated group. These results suggest that LPS causes the production of other mediator(s), in addition to NO, which also stimulates soluble GC (i.e., increases the formation of cGMP) and then activates the large-conductance KCa channels in the vascular smooth muscle causing vascular hyporeactivity.

Animals↗

PubMed1998

Garlic prevents hypoxic pulmonary hypertension in rats.

Hypoxic pulmonary vasoconstriction underlies the development of high-altitude pulmonary edema. Anecdotal observations suggest a beneficial effect of garlic in preventing high-altitude symptoms. To determine whether garlic influences pulmonary vasoconstriction, we assessed the effect of garlic on pulmonary pressures in rats subjected to alveolar hypoxia and on vasoconstriction in isolated pulmonary arterial rings. Garlic gavage (100 mg/kg body wt) for 5 days resulted in complete inhibition of acute hypoxic pulmonary vasoconstriction compared with the control group. No difference in mean arterial pressure or heart rate response to hypoxia was seen between the groups. Garlic solution resulted in a significant dose-dependent vasorelaxation in both endothelium-intact and mechanically endothelium-disrupted pulmonary arterial rings. The administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) inhibited the vasodilatory effect of garlic by 80%. These studies document that garlic blocks hypoxic pulmonary hypertension in vivo and demonstrate a combination of endothelium-dependent and -independent mechanisms for the effect in pulmonary arterial rings.

Acetylcholine↗

PubMed1998

Tracheal agenesis with multiple congenital anomalies: a case report.

Tracheal agenesis (TA) is a rare congenital anomaly that is incompatible with prolonged life. It may occur alone or with other associated anomalies. A term infant presented with cyanosis, hypotonia, absence of crying and respiratory distress at birth. Intubation was difficult. Esophageal intubation was performed under laryngoscopy. As TA was suspected, a bronchoscopy was performed and the infant was found to have a normal epiglottis and vocal cords; however, there was no trachea. Cardiorespiratory deterioration developed and the patient died on the night of the second day at the postnatal age of 41 hours. Tracheal agenesis was confirmed at autopsy. Associated anomalies included bronchoesophageal fistula, double outlet of the right ventricle with ventricular septal defect, bicuspid pulmonary valve, single lobe of the right lung, imperforate anus and a rectourethral fistula. According to development theory, tracheal agenesis and VACTERL (vertebral defects, anal atresia, cardiovascular defects, tracheoesophageal fistula, radial dysplasia or renal defects and limb defects association may result from a mesodermal deficiency caused by abnormal blastogenesis.

Abnormalities, Multiple↗

PubMed1998

Symptomatic patent ductus arteriosus in very low birth weight infants.

BACKGROUND: Premature neonatal survival rates have increased significantly. The diagnosis of patent ductus arteriosus (PDA) has also increased. In this paper, we present our experience of incidence, clinical features and outcome of the treatment of symptomatic PDA in very low birth weight infants. METHODS: From January 1990 to December 1995, 181 premature infants with birth weight less than 1,500 g were admitted to the Neonatal Intensive Care Unit (NICU) of Veterans General Hospital-Taipei. Thirty-seven were diagnosed to have symptomatic PDA. By reviewing hospital records, the clinical features and outcome of treatment of these infants were analyzed retrospectively. RESULTS: The incidence of symptomatic PDA was 20.9% and 21.4% in infants with birth weight less than or equal to 1,000 g, 1,001-1,500 g, respectively. The mean age at diagnosis of infants with symptomatic PDA was significantly less than those without symptoms (3.6 +/- 2.9 days vs 9.6 +/- 17.2 days, p = 0.044, 95% CI = 0.2-11.8). With fluid restriction and diuretic therapy, asymptomatic patients had a higher spontaneous ductal closure rate than symptomatic patients (58.3% vs 10.8%, p < 0.001, 95% CI = 17.9-77.1%). Thirty-two (97.0%) infants with symptomatic PDA responded to indomethacin therapy. However, four infants (12.1%) had recurrence. These four infants and a nonresponder received surgical ligation of the PDA and survived. There were four deaths. The reasons for death were respiratory failure in two, sepsis in one and necrotizing enterocolitis with intestinal perforation in one. CONCLUSIONS: Conservative medical management such as fluid restriction and diuretics are often adequate for asymptomatic PDA. However, since symptomatic PDA tends not to close spontaneously, patients should be treated with indomethacin if ductal shunting compromises cardiopulmonary function.

Ductus Arteriosus, Patent↗