ABSTRACT
BACKGROUND: The TOPP Registry has been designed to provide epidemiologic, diagnostic, clinical, and outcome data on children with pulmonary hypertension (PH) confirmed by heart catheterisation (HC). This study aims to identify important characteristics of the haemodynamic profile at diagnosis and HC complications of paediatric patients presenting with PH. METHODS AND RESULTS: HC data sets underwent a blinded review for confirmation of PH (defined as mean pulmonary arterial pressure ≥ 25 mmHg, pulmonary capillary wedge pressure ≤ 12 mmHg and pulmonary vascular resistance index [PVRI] of >3 WU × m(2)). Of 568 patients enrolled, 472 who fulfilled the inclusion criteria and had sufficient data from HC were analysed. A total of 908 diagnostic and follow-up HCs were performed and complications occurred in 5.9% of all HCs including five (0.6%) deaths. General anaesthesia (GA) was used in 53%, and conscious sedation in 47%. Complications at diagnosis were more likely to occur if GA was used (p=0.04) and with higher functional class (p=0.02). Mean cardiac index (CI) was within normal limits at diagnosis when analysed for the entire group (3.7 L/min/m(2); 95% confidence interval 3.4-4.1), as was right atrial pressure despite a severely increased PVRI (16.6 WU × m(2,) 95% confidence interval 15.6-17.76). However, 24% of the patients had a CI of <2.5L/min/m(2) at diagnosis. A progressive increase in PVRI and decrease in CI was observed with age (p<0.001). CONCLUSION: In TOPP, haemodynamic assessment was remarkable for preserved CI in the majority of patients despite severely elevated PVRI. HC-related complication incidence was 5.9%, and was associated with GA and higher functional class.
Subject(s)
Hemodynamics/physiology , Hypertension, Pulmonary/physiopathology , Outcome Assessment, Health Care , Pulmonary Artery/physiopathology , Registries , Risk Assessment/methods , Adolescent , Cardiac Catheterization/adverse effects , Child , Child, Preschool , Female , Follow-Up Studies , Global Health , Humans , Hypertension, Pulmonary/diagnosis , Infant , Male , Prospective Studies , Pulmonary Artery/injuries , Time FactorsABSTRACT
PREMISE OF THE STUDY: Although long-distance pollen movement is common in wind-pollinated trees, barriers to gene flow may occur in species that have discontinuous ranges or are confined to certain habitat types. We investigated the genetic structure of Quercus lobata Née populations throughout much of their range in California. We assessed the connectivity of populations and determined if barriers to gene flow occurred, and if so, if they corresponded to landscape features. METHODS: We collected leaf samples from 270 trees from 12 stands of Quercus lobata and genotyped these trees using eight polymorphic microsatellite loci. Genetic structure and clustering was evaluated using genetic distance methods, Bayesian clustering approaches, and network analysis of spatial genetic structure. KEY RESULTS: The southernmost population of Quercus lobata sampled from the Santa Monica area comprised a separate genetic cluster from the rest of the species, suggesting that Transverse Ranges such as the San Gabriel Mountains limit gene flow. Population differentiation among the other sites was small but significant. Network analysis reflected higher connectivity among populations along the Central Coast range, with few connections spanning the dry, low Central Valley. CONCLUSIONS: While long distance pollen movement has been shown to be common in oaks, on larger spatial scales, topographic features such as mountain ranges and the large, flat Central Valley of California limit gene flow. Such landscape features explain gene flow patterns much better than geographic distance alone.
Subject(s)
Ecosystem , Gene Flow , Microsatellite Repeats , Quercus/genetics , California , Cell Nucleus/geneticsABSTRACT
BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disorder characterised by raised pulmonary artery pressures with pathological changes in small pulmonary arteries. Previous studies have shown that approximately 70% of familial PAH and also 11-40% of idiopathic PAH (IPAH) cases have mutations in the bone morphogenetic protein receptor type II (BMPR2) gene. In addition, mutations in the activin receptor-like kinase 1 (ALK1) gene have been reported in PAH patients. Since both the BMPR2 and ALK1 belonging to the transforming growth factor (TGF)-beta superfamily are known to predispose to PAH, mutations in other genes of the TGF-beta/BMP signalling pathways may also predispose to PAH. METHODS: We screened for mutations in ENDOGLIN(ENG), SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6 and SMAD8 genes, which are involved in the TGF-beta/BMP signallings, in 23 patients with IPAH who had no mutations in BMPR2 or ALK1. RESULTS: A nonsense mutation in SMAD8 designated c.606 C>A, p.C202X was identified in one patient. The father of this patient was also identified as having the same mutation. Functional analysis showed the truncated form of the SMAD8 C202X protein was not phosphorylated by constitutively active ALK3 and ALK1. The SMAD8 mutant was also unable to interact with SMAD4. The response to BMP was analysed using promoter-reporter activities with SMAD4 and/or ca-ALK3. The transcriptional activation of the SMAD8 mutant was inefficient compared with the SMAD8 wild type. CONCLUSION: We describe the first mutation in SMAD8 in a patient with IPAH. Our findings suggest the involvement of SMAD8 in the pathogenesis of PAH.
Subject(s)
Hypertension, Pulmonary/genetics , Smad8 Protein/genetics , Adolescent , Animals , Base Sequence , COS Cells , Cell Line , Child , Child, Preschool , Chlorocebus aethiops , Codon, Nonsense , DNA Mutational Analysis , Female , Humans , Hypertension, Pulmonary/pathology , Hypertension, Pulmonary/physiopathology , Immunoblotting , Immunoprecipitation , Luciferases/genetics , Luciferases/metabolism , Male , Pedigree , Phosphorylation , Protein Binding , Smad8 Protein/metabolism , Transcriptional Activation , TransfectionABSTRACT
OBJECTIVES: This study assessed the BRCA1 gene expression in breast cancer in Kuwait, and compared it with other known prognostic factors for the disease. MATERIALS AND METHODS: Forty-eight random samples of archival paraffin-embedded breast cancer tissues were studied for BRCA1 gene expression. Immunohistochemical method utilizing antibodies against different epitopes on the BRCA1 protein was used to study BRCA1 protein expression. In addition, for 29 patients, reverse transcription-polymerase chain reaction was used to detect BRCA1 mRNA expression. BRCA1 expression was correlated with age, histological type and grade of breast cancer, estrogen and progesterone receptor status, and C-erbB-2 expression. RESULTS: No demonstrable BRCA1 mRNA and protein expression was found in 79 and 83% of the breast cancer tissues, respectively. A positive relationship was demonstrated between lack of BRCA1 (mRNA and protein) expression and high histological grade, negative estrogen and progesterone receptor status, and overexpression of C-erbB-2 in the breast cancer tissues. CONCLUSIONS: The study demonstrated lack of BRCA1 gene expression (mRNA and protein) in the majority of breast cancers in Kuwait and confirmed the inverse relationship between BRCA1 expression and parameters that determine poor prognosis in breast cancer.
Subject(s)
Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genes, BRCA1 , Adult , Aged , Base Sequence , Breast Neoplasms/metabolism , Breast Neoplasms/physiopathology , DNA Primers , Female , Genes, erbB-2 , Humans , Kuwait , Middle Aged , Prognosis , RNA, Messenger/genetics , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Reverse Transcriptase Polymerase Chain ReactionSubject(s)
Chromosome Deletion , Chromosomes, Human, Pair 2 , Hirschsprung Disease/diagnosis , Hirschsprung Disease/genetics , Homeodomain Proteins/genetics , Mutation , Repressor Proteins/genetics , Adult , Child , Child, Preschool , Chromosome Breakage , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/genetics , DNA Mutational Analysis , Female , Humans , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Male , Microcephaly/diagnosis , Microcephaly/genetics , Syndrome , Zinc Finger E-box Binding Homeobox 2ABSTRACT
The epidemiology of Hodgkin's lymphoma (HL) shows wide geographic variation in histological subtypes and in its association with the Epstein-Barr virus (EBV). The proportion of EBV positive HL is low in industrialized countries, high in non-industrialized countries and intermediate in early-industrialized countries. Reports from the Persian Gulf and Middle East are very limited. The aim of this study was to determine the epidemiology of HL in Kuwait, an early-industrialized country in the Persian Gulf, and to delineate the extent of its association with EBV. We reviewed 134 cases of HL for histological classification and demographic data. 107 cases were examined for the presence of EBV using immunohistochemistry (IHC) for the latent membrane protein I (LMPI) and in-situ hybridization (ISH) for EBVencoded RNA (EBER). 70.4% of the patients were males and 29.6% were females. The male: female ratio was 2.4:1. The mean age was 30.6 years (range, 4-71 years). Mixed cellularity HL (MCHL) was the most common subtype (45.5%), followed by nodular sclerosis (37.3%), nodular lymphocyte predominant (6.7%), lymphocyte rich (3%) and lymphocyte depletion (3%). 4.5% of cases were unclassifiable. EBV expression was seen in 56%, was significantly higher in MCHL, in children, and in males. Our findings suggest that the frequency of EBV expression in HL in Kuwait is similar to other early-industrialized countries. Further research from other countries in the Persian Gulf and the Middle East should shed more light on the epidemiology of HL and its relation to EBV in this region.
Subject(s)
Epstein-Barr Virus Infections/epidemiology , Herpesvirus 4, Human/isolation & purification , Hodgkin Disease/epidemiology , Hodgkin Disease/virology , Adolescent , Adult , Aged , Child , Epstein-Barr Virus Infections/metabolism , Female , Herpesvirus 4, Human/genetics , Hodgkin Disease/metabolism , Humans , Immunoenzyme Techniques , In Situ Hybridization , Incidence , Kuwait/epidemiology , Male , Middle Aged , RNA-Binding Proteins/metabolism , Ribosomal Proteins/metabolism , Viral Matrix Proteins/metabolismABSTRACT
The Research Committee of Ministry of Health, Labour and Welfare 'Study of treatment and long-term management in Kawasaki disease' reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.
Subject(s)
Angioplasty, Balloon, Coronary/standards , Coronary Disease/therapy , Mucocutaneous Lymph Node Syndrome/complications , Myocardial Infarction/therapy , Angioplasty, Balloon, Coronary/methods , Combined Modality Therapy , Coronary Disease/etiology , Humans , Myocardial Infarction/etiology , Plasminogen Activators/therapeutic use , Recurrence , Stents , Tissue Plasminogen Activator/therapeutic use , Ultrasonography, InterventionalABSTRACT
OBJECTIVES: This study investigated whether plasma levels of adrenomedullin, a potent vasodilating endogenous neurohumoral mediator, are useful for assessing the severity of primary pulmonary hypertension. METHODS: Seventeen pediatric patients with primary pulmonary hypertension (eight girls, nine boys, mean age 12 +/- 4 years) were enrolled in this study. Thirteen patients in New York Heart Association (NYHA) classes III and IV had been treated with long-term continuous intravenous prostacyclin (PGI2) infusion therapy, and four patients in classes I and II had received beraprost sodium, an oral PGI2 analogue. Blood samples were taken from all patients at the first visit. Plasma levels of atrial and brain natriuretic peptide (ANP, BNP) and endothelin-1, and mature-type adrenomedullin were measured. The relationships were investigated between neurohumoral mediator levels and NYHA class, pulmonary hemodynamics, and exercise capacity assessed by 6-minute walk test. The changes in neurohumoral mediator levels at 1 month, 3 months, and 6 to 12 months were also evaluated in 11 survivors with long-term PGI2 treatment. RESULTS: All neurohumoral mediator levels were positively correlated with severity of NYHA class. Patients in class IV demonstrated significantly elevated neurohumoral mediator levels, except endothelin-1, in comparison with patients in classes I-III. Neurohumoral mediator levels had a significant negative correlation with exercise capacity. Stepwise regression analysis revealed that the BNP to ANP ratio (BNP/ANP) was the most powerful independent factor for total pulmonary resistance (r = 0.85, p = 0.0071) and cardiac index (r = 0.84, p = 0.009). Adrenomedullin was significantly correlated with BNP (r = 0.53, p = 0.03), endothelin-1 (r = 0.66, p = 0.006), and BNP/ANP (r = 0.73, p = 0.0009). ANP and BNP decreased from 196 +/- 213 and 494 +/- 361 pg/ml at baseline to 74 +/- 47 and 153 +/- 133 pg/ml at 1 month, respectively. There was an apparent re-increase in both ANP (187 +/- 194 pg/ml) and BNP (466 +/- 621 pg/ml) at 3 months, regardless of improvement in NYHA class and exercise capacity after long-term PGI2 treatment. In contrast, adrenomedullin decreased from 3.0 +/- 2.2 (baseline) to 1.7 +/- 0.7 fmol/ml at 1 month and 1.6 +/- 0.5 fmol/ml at 3 months. Adrenomedullin was slightly increased at 6-12 months (2.1 +/- 0.9 fmol/ml) without statistical significance. There was a significant relationship between the changes in adrenomedullin at 3 months compared to values at initiation of PGI2 therapy and the changes in mean pulmonary arterial pressure (r = 0.97, p = 0.0041). CONCLUSIONS: Plasma levels of neurohumoral mediators are useful for assessing the severity of primary pulmonary hypertension. In particular, adrenomedullin was valuable for evaluating both cardiac performance and pulmonary hemodynamics after long-term treatment with PGI2 in patients with primary pulmonary hypertension.
Subject(s)
Antihypertensive Agents/administration & dosage , Epoprostenol/analogs & derivatives , Epoprostenol/administration & dosage , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/drug therapy , Peptides/blood , Adolescent , Adrenomedullin , Antihypertensive Agents/pharmacology , Atrial Natriuretic Factor/blood , Child , Child, Preschool , Endothelin-1 , Epoprostenol/pharmacology , Exercise Tolerance/drug effects , Female , Hemodynamics/drug effects , Humans , Infusions, Intravenous , Male , Natriuretic Peptide, Brain/bloodABSTRACT
UNLABELLED: We describe two adolescent girls with a congenital portosystemic shunt who exhibited hyperandrogenism in addition to insulin resistant hyperinsulinaemia. Case 1 was referred to our clinic to undergo a routine clinical work-up prior to tonsillectomy at 14 years of age. Mild liver dysfunction was identified and hypogenesis of the portal vein with a congenital portosystemic shunt diagnosed. Primary amenorrhoea and virilization were evident and an endocrinological evaluation revealed hyperandrogenism and insulin resistant hyperinsulinaemia. Case 2 was referred at 15 years of age because of cardiomegaly. Mild liver dysfunction and hyperbilirubinaemia led to a diagnosis of agenesis of the portal vein with a congenital portosystemic shunt. Virilization was evident and an endocrinological evaluation revealed hyperandrogenism and insulin resistant hyperinsulinaemia. The haemodynamics of these patients were similar to those of secondary portosystemic shunt due to liver cirrhosis, which is often associated with hyperinsulinaemia and/or non-insulin dependent diabetes mellitus. On the other hand, hyperandrogenism is associated with certain insulin-resistant conditions with hyperinsulinaemia, including the polycystic ovary syndrome (PCO). Hyperinsulinaemia is believed to cause hyperandrogenism in patients with PCO by stimulating androgen production in both the ovary and adrenal gland. Therefore, in congenital portosystemic shunts, hyperinsulinaemia is also thought to cause hyperandrogenism due to the same mechanism. CONCLUSION: A certain percentage of female patients with hyperandrogenism, likely including those with polycystic ovary syndrome may also have congenital portosystemic shunts. Our results indicate that serum levels of total bile acids and ammonia are prognostic indicators of this hepatic vascular anomaly.
Subject(s)
Hyperandrogenism/complications , Portal Vein/abnormalities , Vena Cava, Inferior/abnormalities , Adolescent , Adrenocorticotropic Hormone , Androstenedione/blood , Dehydroepiandrosterone/blood , Female , Glucose Tolerance Test , Humans , Hyperandrogenism/blood , Hyperandrogenism/pathology , Hyperinsulinism/blood , Hyperinsulinism/complications , Insulin Resistance , Magnetic Resonance Angiography , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/complicationsABSTRACT
For recent decades, the medical treatment of primary pulmonary hypertension(PH) have shown an improved outcome as a bridge to lung transplantation. Both nitric oxide (NO) and endothelin(ET) have reported as a major vasoactive mediators in initiating PH. NO is a potent vasodilator released from endothelial cells to adjacent smooth muscle cells in vascular wall. Inhalation of NO has exerted dramatic effects with minimum complication for PH patients. ET-1, after binding to ETA receptor, promotes a strong vasoconstriction, cell growth and platelet aggregation. ETB receptor promotes the clearance of circulating ET-1 in the lung, and stimulates the release of NO and PGI2. Therapeutic trials of ETA receptor antagonist and NO donors for PH may be promising because of their direct action against vasoconstriction.
Subject(s)
Endothelins/physiology , Hypertension, Pulmonary/etiology , Nitric Oxide/physiology , Endothelin Receptor Antagonists , Humans , Nitric Oxide/therapeutic use , Protein Isoforms/physiology , Receptors, Endothelin/physiologyABSTRACT
Prostacyclin (PGI2) is a potent and a promising vasodilative agent in the treatment of pulmonary hypertension (PH). Epoprostenol (Flolan), an intravenous PGI2, has been used for PPH, and exerts dramatic effects such as reducing pulmonary vascular resistance and increasing cardiac output leading to an improvement of exercise tolerance. However, continuous i.v. infusion accompanies infection, thrombosis, occlusion, battery problems and variable side effects of PGI2 itself. Uniprost, administered subcutaneously, has a rather long half-life. It also needs an ambulatory infusion pump system. Beraprost, an oral PGI2 analogue, is also effective in mild PH patients. It can be absorbed easily and administered tid, or qid fashion. Inhaled iloprost may be an alternative option, but both iloprost and beraprost require frequent administrations because of their short half-life.
Subject(s)
Antihypertensive Agents/therapeutic use , Epoprostenol/therapeutic use , Hypertension, Pulmonary/drug therapy , Administration, Inhalation , Antihypertensive Agents/administration & dosage , Epoprostenol/administration & dosage , Humans , Iloprost/administration & dosage , Infusions, Intravenous , Injections, SubcutaneousABSTRACT
Female mice lacking the gene encoding the prostaglandin (PG) E(2) receptor subtype EP(2) (EP(2)(-/-)) become pregnant and deliver their pups at term, but with a much reduced litter size. A decrease in ovulation number and a much reduced fertilization rate were observed in EP(2)(-/-) females without difference of the uterus to support implantation of wild-type embryos. Treatment with gonadotropins induced EP(2) mRNA expression in the cumulus cells of ovarian follicles of wild-type mice. The immature cumuli oophori from wild-type mice expanded in vitro in response to both follicle-stimulating hormone and PGE(2), but the response to PGE(2) was absent in those from EP(2)(-/-) mice. Cumulus expansion proceeded normally in preovulatory follicles but became abortive in a number of ovulated complexes in EP(2)(-/-) mice, indicating that EP(2) is involved in cumulus expansion in the oviduct in vivo. No difference in the fertilization rate between wild-type and EP(2)(-/-) mice was found in in vitro studies using cumulus-free oocytes. These results indicate that PGE(2) cooperates with gonadotropin to complete cumulus expansion for successful fertilization.
Subject(s)
Abortion, Spontaneous/genetics , Chorionic Gonadotropin/pharmacology , Infertility, Female/genetics , Ovarian Follicle/metabolism , Receptors, Prostaglandin E/genetics , Receptors, Prostaglandin E/physiology , Animals , Cyclooxygenase 2 , Dinoprostone/pharmacology , Embryo Transfer , Female , Fertilization , Follicle Stimulating Hormone/pharmacology , Gene Expression Regulation/drug effects , In Vitro Techniques , Infertility, Female/physiopathology , Isoenzymes/genetics , Litter Size , Male , Mice , Mice, Knockout , Ovarian Follicle/drug effects , Ovulation , Pregnancy , Prostaglandin-Endoperoxide Synthases/genetics , RNA, Messenger/genetics , Receptors, Prostaglandin E/deficiency , Receptors, Prostaglandin E, EP2 Subtype , Transcription, Genetic/drug effectsABSTRACT
An eight-year-old boy, Noonan syndrome associated with ASD and PS, was referred to our department for surgical repair. During operation, the coronary sinus ostium was not found. Farther more exploration revealed completely unroofed coronary sinus without LSVC. The large ASD (confluent with coronary sinus ASD) was closed with a ePTFE patch. The pulmonary valve was thickened moderately and each commissure was adhesive, but not dysplastic. PS was released with commissurotomy and subpulmonary muscle resection. The postoperative course was uneventful and the patient discharged at 14 postoperative day. At present, he has been followed at outpatient without PS and any sign and symptom of myocardial hypertrophy.
Subject(s)
Coronary Vessel Anomalies/surgery , Heart Septal Defects, Atrial/surgery , Noonan Syndrome/complications , Pulmonary Valve Stenosis/surgery , Cardiac Surgical Procedures/methods , Child , Humans , Male , PolytetrafluoroethyleneABSTRACT
To investigate molecular and clinical aspects of conotruncal anomaly face (CAF), we studied the correlation between deletion size and phenotype and the mode of inheritance in 183 conotruncal anomaly face syndrome (CAFS) patients. Hemizygosity for a region of 22ql1.2 was found in 180 (98%) of the patients with CAFS by fluorescence in situ hybridization (FISH) using the N25(D22S75) DiGeorge critical region (DGCR) probe. No hemizygosity was found in three (2%) of the patients with CAFS by FISH using nine DiGeorge critical region probes and a SD1OP1 probe (DGA II locus). None of these three patients had mental retardation and just one had nasal intonation, which was observed in almost all of the 180 CAFS patients who carried deletions (mental retardation, 92%; nasal voice, 88%). Nineteen of 143 families (13%) had familial CAFS and 16 affected parents (84%) were mothers. Although only two of the affected parents had cardiovascular anomalies, the deletion size in the 16 affected parents and their affected family members, who were studied by FISH analysis, was the same. It indicates that extragenic factors may play a role in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. No familial cases were found among CAFS patients with absent thymus/DiGeorge anomaly (DGA). Also, in all 18 CAFS patients with completely absent thymus/DGA and all 6 CAFS patients with schizophrenia, it was revealed that the deletion was longer distally. A study of the origin of the deletion using microsatellite analyses in 48 de novo patients showed that in 65% of CAFS patients it was maternal, while in 64% of DGA patients it was paternal. The findings of this study indicated that CAF was almost always associated with the deletion of 22ql1.2. As well as the major features of the syndrome, other notable extracardiac anomalies were found to be susceptibility to infection, schizophrenia, atrophy or dysmorphism of the brain, thrombocytopenia, short stature, facial palsy, anal atresia, and mild limb abnormalities.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 22 , Face/abnormalities , Heart Defects, Congenital/genetics , Adolescent , Adult , Cardiovascular Diseases/genetics , Child , Child, Preschool , Chromosome Mapping , Female , Genomic Imprinting , Humans , In Situ Hybridization, Fluorescence , Infant , Karyotyping , Male , Microsatellite Repeats , Nuclear Family , Polymorphism, Genetic , Syndrome , Tetralogy of Fallot/geneticsABSTRACT
During November 1986 and May 1997, 19 patients with total anomalous pulmonary venous connection (TAPVC) underwent repair surgery. 20 operations including two reoperations were performed. 8 of 19 patients were classified as Darling type Ia, 5 as type IIa, 4 as type III and 2 patients were type IV. Two patients were operated under emergency circumstances within 24 hours after admission, 7 patients were after a short term stabilization of 4.4 days, and the other 11 patients received surgical treatment after a mean of 8.8 days as scheduled cases. For the anostomosis, the common pulmonary venous chamber or the vertical vein was connected with the left atrium in type Ia and III cases; in type IIa and IV cases the cut-back method was performed. Persistent pulmonary hypertension and post-operative pulmonary venous obstruction (PVO) affected the post-operative clinical course. Persistent pulmonary hypertension caused the death of one patient with type IIa and III each, just after operation. One type IV patient died 50 days after operation. The autopsy revealed post-operative obstructions of the remote parts of the pulmonary veins on the anostomosis site. Two patients (type IIa, III) successfully underwent reoperation due to PVO. Post-operative cardiac catheterization was performed after 12 month in 12 cases. Persistent pulmonary hypertension was found in 4 patients, and a type III patient was reoperated because of stenosis of the anostomosis site. The other three patients had persistent pulmonary hypertension without any demonstrable PVO. Persistent pulmonary hypertension and PVO are combined as TAPVC complex. The difficulty to reoperated patients with persistent pulmonary hypertension caused by PVO is one major problem. So preoperative prevention of PVO by normalization the morphologic changes of the pulmonary veins by using drugs could be a different view point in TAPVC therapy after the initial operation.
Subject(s)
Postoperative Complications , Pulmonary Veins/abnormalities , Pulmonary Veins/surgery , Pulmonary Veno-Occlusive Disease , Anastomosis, Surgical , Female , Humans , Hypertension, Pulmonary/prevention & control , Infant , Infant, Newborn , Male , Preoperative Care , Pulmonary Veno-Occlusive Disease/prevention & control , Reoperation , Vascular Surgical ProceduresABSTRACT
To investigate the conservation of mechanisms for mesodermal patterning between zebrafish and Xenopus, we isolated two cDNA clones encoding bone morphogenetic protein (BMP)-related proteins from a zebrafish cDNA library. Based on their predicted amino acid sequences, these two clones were designated as zbmp-2 and zbmp-4. Whole-mount in situ hybridization analysis revealed that in gastrula embryo, both genes were localized in the ventral part of the embryo, consistent with the proposed function of Xenopus BMP-4 in ventral mesoderm specification. zbmp-4 expression, however, was also seen in the embryonic shield, the most dorsal mesodermal structure. To examine the ability of zbmp-2 to ventralize mesoderm, we injected synthetic mRNA into zebrafish embryos and found that overexpression of this gene eliminated dorsal structures including notochord at both morphological and molecular level. In contrast, expression of ventral marker gene eve1 was expanded to the dorsal side. These effects are analogous to the ventralization of embryos caused by ectopic xBMP-4 expression. Taken together, one may conclude that the developmental mechanisms for mesodermal patterning regulated by BMPs are evolutionarily conserved between amphibians and teleosts.
Subject(s)
Bone Morphogenetic Proteins/physiology , Mesoderm/physiology , Morphogenesis , Transforming Growth Factor beta , Zebrafish/embryology , Amino Acid Sequence , Animals , Bone Morphogenetic Protein 2 , Bone Morphogenetic Protein 4 , Bone Morphogenetic Proteins/genetics , Cloning, Molecular , DNA, Complementary/genetics , Gastrula/metabolism , Gene Expression Regulation, Developmental , Genes , In Situ Hybridization , Molecular Sequence Data , RNA, Messenger/genetics , Sequence Alignment , Xenopus Proteins , Zebrafish/genetics , Zebrafish ProteinsABSTRACT
In 4 patients with primary pulmonary hypertension, there was a -24% +/- 20% decrease in pulmonary vascular resistance, a significant increase of cardiac index by +27 +/- 14% in all 4 patients; a -15 +/- 12% decrease in pulmonary artery pressure in 3 patients; and in 3 patients with 12% secondary pulmonary hypertension, there was a -24 +/- 14% decrease in pulmonary vascular resistance. Beraprost appears to be effective as a new pulmonary vasodilative agent.
Subject(s)
Epoprostenol/analogs & derivatives , Hemodynamics/drug effects , Hypertension, Pulmonary/physiopathology , Platelet Aggregation Inhibitors/pharmacology , Vasodilator Agents/pharmacology , Adult , Child , Epoprostenol/pharmacology , Epoprostenol/therapeutic use , Female , Humans , Hypertension, Pulmonary/drug therapy , Infant , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Treatment Outcome , Vasodilator Agents/therapeutic useABSTRACT
Prostacyclin (PGI2) is a bioactive substance produced by vascular endothelial cells, which exerts powerful vasodilative and anti-platelet actions. Patients with pulmonary hypertension have an imbalance between vasodilative PGI2 and vasoconstrictive thromboxane B2 (TXB2). Treatment with vasodilative agents is essential for such patients. Continuous intravenous infusion of PGI2 is an effective treatment of primary pulmonary hypertension in terms of exercise capacity and survival rate. We tested a new stable PGI2 analogue, beraprost sodium (Procyclin, Dornar) suitable for oral administration, in patients with primary and secondary pulmonary hypertension. A short-term study of cardiac catheterization in four patients with primary pulmonary hypertension showed a 15 +/- 12% reduction in mean pulmonary artery pressure in three of the four patients, and a 24 +/- 22% decrease in pulmonary vascular resistance in all four patients. Cardiac index increased by 27 +/- 14% in three of the four patients. Among three patients with secondary pulmonary hypertension, there was a 7% reduction in pulmonary artery pressure in one patient, and a 24 +/- 14% decrease in pulmonary vascular resistance in all three patients. In a long-term study (23 +/- 11 months), NYHA functional class improved from 3.0 +/- 0.7 to 2.4 +/- 0.5 in two of the five patients with primary pulmonary hypertension. Although the radiographic cardiothoracic ratio was not significantly improved, cardiac index increased by 78 +/- 60% in four of the five patients. Only two patients, one with primary and one with secondary pulmonary hypertension, died during the long-term follow-up period. Plasma TXB2/6-keto prostaglandin F1 alpha ratio decreased from 8.1 +/- 8.7 to 1.5 +/- 0.4. The optimal dose remains uncertain, but the initial dosage of 40-60 micrograms/day given in three to four doses for adult patients is considered to be acceptable. Side effects such as flushing face, headache, vomiting, and nausea were mild and resolved when the dose was reduced. Oral PGI2, beraprost, appears to be an effective and possibly adequate substitute for intravenous vasodilators in pulmonary hypertension for both short- and long-term management.
Subject(s)
Epoprostenol/analogs & derivatives , Hypertension, Pulmonary/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Vasodilator Agents/therapeutic use , 6-Ketoprostaglandin F1 alpha/blood , Administration, Oral , Adolescent , Adult , Child , Child, Preschool , Epoprostenol/administration & dosage , Epoprostenol/therapeutic use , Female , Humans , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/physiopathology , Infant , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Pulmonary Circulation/drug effects , Pulmonary Wedge Pressure/drug effects , Thromboxane B2/blood , Time Factors , Vascular Resistance/drug effects , Vasodilator Agents/administration & dosageABSTRACT
A 15 month old female, who had suffered from ventricular tachycardia from the prenatal period, experienced cardiac arrest at home. Once she had recovered, ventricular tachycardia occurred repeatedly. She died 7 months after admission. At autopsy, the heart showed many yellowish white nodules in the endocardium. Histologically these nodules consisted of granular or foamy histiocyte-like cells, which had spread to all four chambers. Electron micrographs showed mitochondrial hyperplasia in these cells. The cells had some myofibrils in their cytoplasm. These findings were compatible with histiocytoid cardiomyopathy. Interestingly, the present case showed hypotonia. Her muscle biopsy revealed decreased activity of cytochrome c oxidase, suggesting that histiocytoid cardiomyopathy is related to mitochondrial cytopathy.
Subject(s)
Cardiomyopathies/pathology , Histiocytosis/pathology , Muscle Hypotonia/complications , Cardiomyopathies/complications , Electrocardiography , Electron Transport Complex IV/analysis , Fatal Outcome , Female , Heart Arrest/etiology , Humans , Infant , Microscopy, Electron , Mitochondria/ultrastructure , Muscle Hypotonia/pathology , Muscle, Skeletal/chemistry , Muscle, Skeletal/pathology , Myofibrils/ultrastructure , Tachycardia, Ventricular/etiologyABSTRACT
A 1-year-and-9-months old boy with gait disturbance during the 3rd week of Kawasaki disease (KD) was described. He had been previously healthy, and developed high fever and rash. The diagnosis of KD was based on 5 of 6 major criteria on the 3rd clinical day. He was initially treated with intravenous gamma-globulin 400 mg/kg/day for five days. On the 17th clinical day, the patient developed gait disturbance after most clinical signs disappeared. His gait was wide- based and unstable. Generalized hypotonia with poor traction response was also seen. Pyramidal tract signs including exaggerated patellar and Achilles tendon reflexes and positive bilateral Mendel-Bechterew reflex were presented. Cerebrospinal fluid was normal. Brain CT, MRI, and 123I-IMP SPECT images were normal without broad hemorrhage or infarction of the cerebral parenchyma. Gait disturbance recovered spontaneously within one month without any sequelae.