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1.
Ann R Coll Surg Engl ; 106(4): 321-328, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38555869

ABSTRACT

Genomics is a crucial part of managing surgical disease. This review focuses on some of the genomic advances that are available now and looks to the future of their application in surgical practice. Whole-genome sequencing enables unbiased coverage across the entire human genome of approximately three billion base pairs. Newer technologies, such as those that permit long-read sequence analysis, provide additional information in longer phased fragment and base pair epigenomic (methylomic) data. Whole-genome sequencing is currently available in England for cancers in children, teenagers and young adults, central nervous system tumours, sarcoma and haematological malignancies. Circulating tumour DNA (ctDNA), immunotherapy and pharmacogenomics have emerged as groundbreaking approaches in the field of cancer treatment. These are now revolutionising the way oncologists and surgeons approach curative cancer surgery. Cancer vaccines offer an innovative approach to reducing recurrence after surgery by priming the immune system to trigger an immune response. The Cancer Vaccine Launch Pad project facilitates cancer vaccine studies in England. The BNT122-01 trial is recruiting patients with ctDNA-positive high-risk colorectal cancer after surgery to assess the impact of cancer vaccines. The evolving landscape of cancer treatment demands a dynamic and integrated approach from the surgical multidisciplinary team. Immunotherapy, ctDNA, pharmacogenomics, vaccines, mainstreaming and whole-genome sequencing are just some of the innovations that have the potential to redefine the standards of care. The continued exploration of these innovative diagnostics and therapies, the genomic pathway evolution and their application in diverse cancer types highlights the transformative impact of precision medicine in surgery.


Subject(s)
Cancer Vaccines , Circulating Tumor DNA , Neoplasms , Surgeons , Child , Humans , Adolescent , Circulating Tumor DNA/genetics , Genomics
2.
Ultrasound Obstet Gynecol ; 59(5): 633-641, 2022 05.
Article in English | MEDLINE | ID: mdl-34605096

ABSTRACT

OBJECTIVES: To review our experience with fetal aortic valvuloplasty (FAV) in fetuses with critical aortic stenosis (CAS) and evolving hypoplastic left heart syndrome (eHLHS), including short- and medium-term postnatal outcome, and to refine selection criteria for FAV by identifying preprocedural predictors of biventricular (BV) outcome. METHODS: This was a retrospective review of all fetuses with CAS and eHLHS undergoing FAV at our center between December 2001 and September 2020. Echocardiograms and patient charts were analyzed for pre-FAV ventricular and valvular dimensions and hemodynamics and for postnatal procedures and outcomes. The primary endpoints were type of circulation 28 days after birth and at 1 year of age. Classification and regression-tree analysis was performed to investigate the predictive capacity of pre-FAV parameters for BV circulation at 1 year of age. RESULTS: During the study period, 103 fetuses underwent 125 FAVs at our center, of which 87.4% had a technically successful procedure. Technical success per fetus was higher in the more recent period (from 2014) than in the earlier period (96.2% (51/53) vs 78.0% (39/50); P = 0.0068). Eighty fetuses were liveborn after successful intervention and received further treatment. BV outcome at 1 year of age was achieved in 55% of liveborn patients in our cohort after successful FAV, which is significantly higher than the BV-outcome rate (23.7%) in a previously published natural history cohort fulfilling the same criteria for eHLHS (P = 0.0015). Decision-tree analysis based on the ratio of right to left ventricular (RV/LV) length combined with LV pressure (mitral valve regurgitation maximum velocity (MR-Vmax)) had a sensitivity of 96.97% and a specificity of 94.44% for predicting BV outcome without signs of pulmonary arterial hypertension at 1 year of age. The highest probability for a BV outcome was reached for fetuses with a pre-FAV RV/LV length ratio of < 1.094 (96.4%) and for those fetuses with a RV/LV length ratio ≥ 1.094 to < 1.135 combined with a MR-Vmax of ≥ 3.14 m/s (100%). CONCLUSIONS: FAV could be performed with high success rates and an acceptable risk with improving results after a learning curve. Pre-FAV RV/LV length ratio combined with LV pressure estimates were able to predict a successful BV outcome at 1 year of age with high sensitivity and specificity. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Aortic Valve Stenosis , Balloon Valvuloplasty , Hypoplastic Left Heart Syndrome , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Balloon Valvuloplasty/methods , Female , Fetal Heart/diagnostic imaging , Gestational Age , Humans , Pregnancy , Retrospective Studies , Treatment Outcome , Ultrasonography, Prenatal
3.
Ann Oncol ; 30(3): 456-463, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30452544

ABSTRACT

BACKGROUND: Glioblastoma is the most common and aggressive adult brain malignancy against which conventional surgery and chemoradiation provide limited benefit. Even when a good treatment response is obtained, recurrence inevitably occurs either locally (∼80%) or distally (∼20%), driven by cancer clones that are often genomically distinct from those in the primary tumour. Glioblastoma cells display a characteristic infiltrative phenotype, invading the surrounding tissue and often spreading across the whole brain. Cancer cells responsible for relapse can reside in two compartments of residual disease that are left behind after treatment: the infiltrated normal brain parenchyma and the sub-ventricular zone. However, these two sources of residual disease in glioblastoma are understudied because of the difficulty in sampling these regions during surgery. PATIENT AND METHODS: Here, we present the results of whole-exome sequencing of 69 multi-region samples collected using fluorescence-guided resection from 11 patients, including the infiltrating tumour margin and the sub-ventricular zone for each patient, as well as matched blood. We used a phylogenomic approach to dissect the spatio-temporal evolution of each tumour and unveil the relation between residual disease and the main tumour mass. We also analysed two patients with paired primary-recurrence samples with matched residual disease. RESULTS: Our results suggest that infiltrative subclones can arise early during tumour growth in a subset of patients. After treatment, the infiltrative subclones may seed the growth of a recurrent tumour, thus representing the 'missing link' between the primary tumour and recurrent disease. CONCLUSIONS: These results are consistent with recognised clinical phenotypic behaviour and suggest that more specific therapeutic targeting of cells in the infiltrated brain parenchyma may improve patient's outcome.


Subject(s)
Clonal Evolution/genetics , Exome Sequencing , Glioblastoma/genetics , Neoplasm, Residual/genetics , Brain/metabolism , Brain/surgery , Female , Genome, Human/genetics , Glioblastoma/pathology , Glioblastoma/surgery , Humans , Male , Mutation/genetics , Neoplasm Proteins/genetics , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm, Residual/pathology , Neoplasm, Residual/surgery , Phenotype , Phylogeny , Polymorphism, Single Nucleotide
4.
Ultrasound Obstet Gynecol ; 52(2): 230-237, 2018 08.
Article in English | MEDLINE | ID: mdl-29569770

ABSTRACT

OBJECTIVE: To assess the immediate effects of fetal pulmonary valvuloplasty on right ventricular (RV) size and function as well as in-utero RV growth and postnatal outcome. METHODS: Patients with pulmonary atresia with intact ventricular septum (PAIVS) or critical pulmonary stenosis (CPS) who underwent fetal pulmonary valvuloplasty at our center between October 2000 and July 2017 were included. Echocardiographic data obtained before and after the procedure were analyzed retrospectively (median interval after intervention, 1 (range, 1-3) days) for ventricular and valvular dimensions and ratios, RV filling time (duration of tricuspid valve (TV) inflow/cardiac cycle length), TV velocity time integral (TV-VTI) × heart rate (HR) and tricuspid regurgitation (TR) velocity. Longitudinal data were collected from only those fetuses followed up in our center. Outcome was assessed using the scoring system as described by Roman et al. for non-biventricular outcome. RESULTS: Thirty-five pulmonary valvuloplasties were performed in our institution on 23 fetuses with PAIVS (n = 15) or CPS (n = 8). Median gestational age at intervention was 28 + 4 (range, 23 + 6 to 32 + 1) weeks. No fetal death occurred. Immediately after successful intervention, RV/left ventricular length (RV/LV) ratio (P ≤ 0.0001), TV/mitral valve annular diameter (TV/MV) ratio (P ≤ 0.001), RV filling time (P ≤ 0.00001) and TV-VTI × HR (P ≤ 0.001) increased significantly and TR velocity (P ≤ 0.001) decreased significantly. In fetuses followed longitudinally to delivery (n = 5), RV/LV and TV/MV ratios improved further or remained constant until birth. Fetuses with unsuccessful intervention (n = 2) became univentricular, all others had either a biventricular (n = 15), one-and-a-half ventricular (n = 3) or still undetermined (n = 3) outcome. Five of nine fetuses with a predicted non-biventricular outcome, in which the procedure was successful, became biventricular, while two of nine had an undetermined circulation. CONCLUSION: In selected fetuses with PAIVS or CPS, in-utero pulmonary valvuloplasty led immediately to larger RV caused by reduced afterload and increased filling, thus improving the likelihood of biventricular outcome even in fetuses with a predicted non-biventricular circulation. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Balloon Valvuloplasty , Coronary Circulation/physiology , Fetal Heart/physiopathology , Heart Defects, Congenital/surgery , Pulmonary Atresia/surgery , Pulmonary Valve Stenosis/surgery , Female , Gestational Age , Heart Defects, Congenital/embryology , Heart Defects, Congenital/physiopathology , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome , Pulmonary Atresia/embryology , Pulmonary Atresia/physiopathology , Pulmonary Valve Stenosis/embryology , Pulmonary Valve Stenosis/physiopathology , Retrospective Studies , Ultrasonography, Prenatal
5.
Waste Manag ; 59: 149-159, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27818071

ABSTRACT

In many nations industrial scale AD of non-agricultural waste materials (such as MSW) has not yet reached its full potential, often constrained by the lack of secure, inexpensive, high quality AD feedstocks, and markets for the resulting digestate material. We tested the output material of a high throughput novel industrial process to define its potential as an AD feedstock (based on quality and consistency). This process, designed to circumvent the constraints of source segregation while still generating segregated waste streams, resulted in the production of a temporally homogenous fibrous material with: an average moisture content of 44.2 (±2.33)%; C:N ratio of ∼32.9:1 (±3.46:1), C:P ratio of ∼228:1 and gross calorific value of 17.4 (±0.29)MJ/kg(DM). This material provided a CH4 yield of between 201 and 297m3 CH4/tonne(DM) (271-401m3CH4/tonne(vs)) comparable to commonly used AD feedstocks. Material contaminant levels were temporally consistent (P>0.05), (average values being Cd 0.63 (±0.19), Cu 56.3 (±7.45), Crtot 51.4 (±4.41), Hg<0.3, Ni 28.9 (±5.17), Pb 79.2 (±23.71), Zn 202 (±44.5), total polyaromatic hydrocarbons (PAH) 2.2 (±0.3), and total polychlorinated biphenyls (PCB) (<0.2)mg/kg(DM)). Calculated digestate contaminant levels were below the median contaminant threshold limits for anaerobic digestates of all countries within the European Union i.e. of Cd 3.35, Cu 535, Crtot 535, Hg 8.15, Ni 185, Pb 397.5, Zn 2100mg/kg(DM). We suggest that novel high throughput processes that produce high quality AD feedstocks, may have a place in further diversion of waste from landfill.


Subject(s)
Refuse Disposal/methods , Soil , Waste Disposal Facilities , Anaerobiosis , Biofuels , Cities , Escherichia coli , Europe , Gases , Methane/chemistry , Salmonella , Solid Waste , Spectroscopy, Fourier Transform Infrared , Temperature
6.
Ultrasound Obstet Gynecol ; 44(5): 538-44, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24975801

ABSTRACT

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.


Subject(s)
Aortic Valve Stenosis/surgery , Decision Making , Fetal Diseases/surgery , Hypoplastic Left Heart Syndrome/prevention & control , Patient Care Team/standards , Professional Practice/standards , Aortic Valve Stenosis/embryology , Consensus , Humans , Hypoplastic Left Heart Syndrome/embryology , Organizational Policy
8.
J Bacteriol ; 191(20): 6415-24, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19684142

ABSTRACT

The regulation of acid production in and the tolerance to low pH of the cariogenic bacterium Streptococcus mutans have garnered considerable attention since both of these properties contribute substantially to the virulence of this organism. Frequent or prolonged exposure to acid end products, mainly lactic acid, that are present following the consumption of dietary sugars erodes the dental enamel, thereby initiating dental caries. Here we report the involvement of the S. mutans VicK sensor kinase in both the acidogenicity and the aciduricity of this bacterium. When cultures were supplemented with glucose, the glycolytic rate of a VicK null mutant was significantly decreased compared to the glycolytic rate of the wild type (P < 0.05), suggesting that there was impaired acid production. Not surprisingly, the VicK deletion mutant produced less lactic acid, while an acid tolerance response assay revealed that loss of VicK significantly enhanced the survival of S. mutans (P < 0.05). Compared to the survival rates of the wild type, the survival rates of the VicK-deficient mutant were drastically increased when cultures were grown at pH 3.5 with or without preexposure to a signal pH (pH 5.5). Global transcriptional analysis using DNA microarrays and S. mutans wild-type UA159 and VicK deletion mutant strains grown at neutral and low pH values revealed that loss of VicK significantly affected expression of 89 transcripts more than twofold at pH 5.5 (P < 0.001). The affected transcripts included genes with putative functions in transport and maintenance of cell membrane integrity. While our results provide insight into the acid-inducible regulon of S. mutans, here we imply a novel role for VicK in regulating intracellular pH homeostasis in S. mutans.


Subject(s)
Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial/physiology , Streptococcus mutans/metabolism , Adaptation, Physiological , Bacterial Proteins/genetics , Culture Media/chemistry , Gene Deletion , Gene Expression Profiling , Hydrogen-Ion Concentration , Streptococcus mutans/genetics , Transcription, Genetic
9.
Microbiology (Reading) ; 155(Pt 9): 2907-2918, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19497950

ABSTRACT

Enterohaemorrhagic Escherichia coli (EHEC) O157 : H7 is naturally exposed to a wide variety of stresses including gastric acid shock, and yet little is known about how this stress influences virulence. This study investigated the impact of acid stress on several critical virulence properties including survival, host adhesion, Shiga toxin production, motility and induction of host-cell apoptosis. Several acid-stress protocols with relevance for gastric passage as well as external environmental exposure were included. Acute acid stress at pH 3 preceded by acid adaptation at pH 5 significantly enhanced the adhesion of surviving organisms to epithelial cells and bacterial induction of host-cell apoptosis. Motility was also significantly increased after acute acid stress. Interestingly, neither secreted nor periplasmic levels of Shiga toxin were affected by acid shock. Pretreatment of bacteria with erythromycin eliminated the acid-induced adhesion enhancement, suggesting that de novo protein synthesis was required for the enhanced adhesion of acid-shocked organisms. DNA microarray was used to analyse the transcriptome of an EHEC O157 : H7 strain exposed to three different acid-stress treatments. Expression profiles of acid-stressed EHEC revealed significant changes in virulence factors associated with adhesion, motility and type III secretion. These results document profound changes in the virulence properties of EHEC O157 : H7 after acid stress, provide a comprehensive genetic analysis to substantiate these changes and suggest strategies that this pathogen may use during gastric passage and colonization in the human gastrointestinal tract.


Subject(s)
Escherichia coli Infections/microbiology , Escherichia coli O157/pathogenicity , Stress, Physiological , Apoptosis , Bacterial Adhesion/drug effects , Cell Line , Epithelial Cells/microbiology , Epithelial Cells/physiology , Erythromycin/pharmacology , Escherichia coli Infections/metabolism , Escherichia coli O157/drug effects , Escherichia coli O157/physiology , Gene Expression Profiling , Host-Pathogen Interactions/drug effects , Humans , Hydrogen-Ion Concentration , Protein Synthesis Inhibitors/pharmacology , Shiga Toxins/biosynthesis , Virulence , Virulence Factors/biosynthesis , Virulence Factors/genetics
10.
J Magn Reson ; 193(2): 274-85, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18550402

ABSTRACT

We describe the design and operation of an open-access, very-low-field, magnetic resonance imaging (MRI) system for in vivo hyperpolarized 3He imaging of the human lungs. This system permits the study of lung function in both horizontal and upright postures, a capability with important implications in pulmonary physiology and clinical medicine, including asthma and obesity. The imager uses a bi-planar B(0) coil design that produces an optimized 65 G (6.5 mT) magnetic field for 3He MRI at 210 kHz. Three sets of bi-planar coils produce the x, y, and z magnetic field gradients while providing a 79-cm inter-coil gap for the imaging subject. We use solenoidal Q-spoiled RF coils for operation at low frequencies, and are able to exploit insignificant sample loading to allow for pre-tuning/matching schemes and for accurate pre-calibration of flip angles. We obtain sufficient SNR to acquire 2D 3He images with up to 2.8mm resolution, and present initial 2D and 3D 3He images of human lungs in both supine and upright orientations. 1H MRI can also be performed for diagnostic and calibration reasons.


Subject(s)
Helium , Image Enhancement/instrumentation , Image Interpretation, Computer-Assisted/instrumentation , Lung/anatomy & histology , Magnetic Resonance Imaging/instrumentation , Posture , Transducers , Equipment Design , Equipment Failure Analysis , Humans , Imaging, Three-Dimensional/instrumentation , Isotopes
11.
Lett Appl Microbiol ; 47(5): 439-44, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19146535

ABSTRACT

AIMS: To identify the genes regulated by RR11, the regulator of the Streptococcus mutans HK/RR11 two-component system. METHODS AND RESULTS: The S. mutans RR11-encoding gene was inactivated, and the effects of gene disruption on the cell's ability to form biofilms under stresses and acquire extracellular DNA were tested. Biofilm was reduced in cells lacking RR11 following exposure to oxidative stress. RR11-defective cells showed approx. 20-fold reduction in transformation efficiency. Microarray used to decipher the RR11-regulated genes in biofilm showed that approx. 5% of the UA159 genome underwent a significant change in expression. RR11 was found to regulate 174 genes, including genes involved in competence, stress-response and cell division. CONCLUSIONS: Target genes controlled by RR11during biofilm growth have been identified by a comparison of transcriptional profiles between an RR11 defective mutant and the parental strain. The results demonstrated that RR11 is involved in the control of diverse cellular processes, including the formation of biofilm under oxidative stress and development of genetic competence. SIGNIFICANCE AND IMPACT OF THE STUDY: The regulator of HK/RR11 system controls a large regulon and is an important regulator involved in stress response during S. mutans biofilm growth enabling the survival and persistence of its progeny in the microbial community.


Subject(s)
Bacterial Proteins/physiology , Biofilms/growth & development , Gene Expression Regulation, Bacterial , Oxidative Stress , Streptococcus mutans/physiology , Transformation, Bacterial , Bacterial Proteins/genetics , Gene Expression Profiling , Gene Knockout Techniques , Oligonucleotide Array Sequence Analysis , Signal Transduction
12.
Lett Appl Microbiol ; 45(4): 398-404, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17897382

ABSTRACT

AIM: To assess potential function of each two-component signal transduction system in the expression of Streptococcus mutans virulence properties. METHODS AND RESULTS: For each two-component system (TCS), the histidine kinase-encoding gene was inactivated by a polymerase chain reaction (PCR)-based deletion strategy and the effects of gene disruption on the cell's ability to form biofilms, become competent, and tolerate acid, osmotic, and oxidative stress conditions were tested. Our results demonstrated that none of the mutations were lethal for S. mutans. The TCS-2 (CiaRH) is involved in biofilm formation and tolerance to environmental stresses, the TCS-3 (ScnRK-like) participates in the survival of cells at acidic pH, and the TCS-9 affects the acid tolerance response and the process of streptococcal competence development. CONCLUSIONS: Our results confirmed the physiological role of the TCS in S. mutans cellular function, in particular the SncRK-like TCS and TCS-9 as they may represent new regulatory systems than can be involved in S. mutans pathogenesis. SIGNIFICANCE AND IMPACT OF THE STUDY: Multiple TCS govern important biological parameters of S. mutans enabling its survival and persistence in the biofilm community.


Subject(s)
Biofilms/growth & development , Signal Transduction , Streptococcus mutans/physiology , Streptococcus mutans/pathogenicity , Gene Deletion , Mutagenesis, Insertional , Streptococcus mutans/genetics , Virulence
13.
Clin Res Cardiol ; 96(10): 723-9, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17676353

ABSTRACT

BACKGROUND: The arterial switch operation (ASO) has become the treatment of choice in patients with simple or complex transposition of the great arteries (TGA). The purpose of this study was to assess early and mid-term outcome after ASO in a single centre. PATIENTS AND METHODS: Between 1995 and December 2005, 114 consecutive patients underwent an ASO at our institution, performed by one single surgeon. Patients charts, surgical reports and echocardiograms were retrospectively reviewed. Patients were analyzed in 3 different groups: Group I consisted of 77 neonates with TGA and intact ventricular septum, group II of 13 patients with TGA and ventricular septal defect which had to be closed surgically and group III of 24 patients with various forms of TGA in a complex setting. The patient's median weight was 3.23 kg (1.65-8.30). Twenty-five neonates were born preterm, 18 were diagnosed prenatally. Median follow-up time was 20.7 months (0.3-128.6). RESULTS: The thirty day mortality was 1.75% (2/114), late mortality 0.88% (1/112) accounting for an overall mortality of 2.63%. There was only one early coronary event and so far no late events. Ten of 111 survivors required reoperation, all but 1 from group III. Prevalence of supravalvular pulmonary stenosis was 4.7%. Freedom from reoperation at 5 years of follow-up time was 87.5%. One patient required permanent pacing, no other late arrhythmias occurred. In our series the only risk factor for increased mortality and morbidity was a body weight of less than 2500 g at the time of operation. No better outcome could be demonstrated in the prenatally diagnosed patients. CONCLUSION: The ASO can be performed safely and with low mortality and morbidity even in patients with complex TGA. Follow-up of these patients is required to detect residual problems like supravalvular pulmonary stenosis, coronary problems, arrhythmias and aortic valve dysfunction.


Subject(s)
Cardiac Surgical Procedures/methods , Transposition of Great Vessels/surgery , Female , Follow-Up Studies , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Male , Postoperative Complications/etiology , Prenatal Diagnosis , Tachycardia/etiology , Transposition of Great Vessels/diagnosis , Transposition of Great Vessels/mortality , Treatment Outcome
15.
Br J Anaesth ; 97(4): 545-52, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16873390

ABSTRACT

BACKGROUND: The goal of the study was to determine activated thrombelastographic (TEG(R)) parameters with the rotational TEG(R) (ROTEG or ROTEM) device (Pentapharm GmbH, Munich, Germany) in neonates and infants <1 yr with complex congenital heart disease (CCHD) and to compare them with those of healthy children. METHODS: A total of 59 children were included: Group I (Gr I) 24 children, ASA I, scheduled for minor surgery; and Group II (Gr II) 35 children with CCHD, ASA III-IV, scheduled for cardiac surgery. Each group was subdivided into four age groups. Blood samples were obtained before the surgical procedure. RESULTS: Statistically significant differences (two-way anova analysis) between Gr I and Gr II [mean (SD); P-value] were found in INTEG-CT [Gr I 175(19), Gr II 271(162); P=0.049], EXTEG-MCF [Gr I 63(8), Gr II 56(8); P=0.013], EXTEG-MCE [Gr I 186(65), Gr II 137(41); P=0.003], FIBTEG-MCF [Gr I 24(7), Gr II 19(5); P=0.012], FIBTEG-MCE [Gr I 32(13), Gr II 24(8); P=0.012] and EXTEG-MCE-FIBTEG-MCE [Gr I 155(55), Gr II 113(37); P=0.003]. Clotting time via contact activation was prolonged in Gr II and varied widely, mainly in the age group 0-1 month and to a lesser extent in 1-3 months, and maximum clot firmness was reduced in the same age groups. In comparison with Gr II, the healthy children showed relatively homogenous TEG values with a tendency to hypercoagulability; the maximum was found in age group 1-3 months, decreasing towards adult values in the course of the first year of life. CONCLUSIONS: These preliminary TEG results indicate that the coagulation-fibrinolytic system in CCHD patients <1 yr is functionally intact and balanced but at a lower level than in healthy children. This could be interpreted as a reduction in the haemostatic potential with less reserve.


Subject(s)
Blood Coagulation , Heart Defects, Congenital/blood , Thrombelastography , Aging/blood , Female , Fibrinolysis , Heart Defects, Congenital/surgery , Humans , Infant , Infant, Newborn , Male , Preoperative Care/methods , Prospective Studies
16.
Article in English | MEDLINE | ID: mdl-20354575

ABSTRACT

We describe a prototype system built to allow open-access very-low-field MRI of human lungs using laser-polarized (3)He gas. The system employs an open four-coil electromagnet with an operational B(0) field of 4 mT, and planar gradient coils that generate gradient fields up to 0.18 G/cm in the x and y direction and 0.41 G/cm in the z direction. This system was used to obtain (1)H and (3)He phantom images and supine and upright (3)He images of human lungs. We include discussion on challenges unique to imaging at 50 -200 kHz, including noise filtering and compensation for narrow-bandwidth coils.

17.
Eur J Anaesthesiol ; 22(4): 293-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15892408

ABSTRACT

BACKGROUND AND OBJECTIVE: To prevent neurological complications, low-flow antegrade cerebral perfusion (ACP) is used during repair of complex congenital heart defects. To overcome technical problems, continuous monitoring of cerebral blood flow and oxygenation is mandatory. The aim of the study was to evaluate the effect of different ACP flow rates on cerebral oxygen saturation obtained by near infrared spectroscopy. METHODS: Ten consecutive neonates undergoing Norwood stage I were included. In addition to near infrared spectroscopy (Invos 5100; Somanetics Corp., USA) on both hemispheres, mean arterial pressure and transcranial Doppler flow velocity were measured continuously and arterial and jugular venous oxygen saturation intermittently. Cerebral oxygen extraction ratio was calculated. Measurement points were obtained after starting bypass, during ACP with flow rates of 30, 20 and 10 mL kg(-1) min(-1) and immediately after ACP. ANOVA and Tukey-Kramer multiple comparison test were used for statistics. RESULTS: The near infrared spectroscopy signal could be obtained in all children at all measurement points, whereas transcranial Doppler failed in 1 neonate at a flow rate of 30 mL kg(-1)min(-1), in 3 neonates at 20 mL kg(-1) min(-1) and in 4 neonates at 10 mL kg(-1)min(-1). With the reduction of flow there was a significant decrease of cerebral oxygen saturation on both hemispheres (right: 78+/-8 to 72+/-9 and 66+/-8, P < 0.001; left: 71+/-7 to 65+/-7 and 60+/-7, P < 0.001), of jugular venous oxygen saturation (94+/-6 to 89+/-13 and 83+/-15, P < 0.001) and a significant increase in oxygen extraction ratio (9.1+/-8 to 14.8+/-14 and 21+/-16, P < 0.001) respectively, for 30, 20, 10 mL kg(-1)min(-1). CONCLUSION: Near infrared spectroscopy reliably detects flow alterations during ACP with profound hypothermia.


Subject(s)
Aortic Arch Syndromes/surgery , Cerebrovascular Circulation/physiology , Monitoring, Intraoperative/methods , Spectroscopy, Near-Infrared/methods , Anesthesia, General , Aortic Arch Syndromes/congenital , Cardiac Catheterization , Female , Humans , Infant, Newborn , Male , Oxygen Consumption/physiology , Prospective Studies , Ultrasonography, Doppler, Transcranial
18.
Magn Reson Med ; 53(4): 745-9, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15799045

ABSTRACT

The human lung and its functions are extremely sensitive to gravity; however, the conventional high-field magnets used for most laser-polarized (3)He MRI of the human lung restrict subjects to lying horizontally. Imaging of human lungs using inhaled laser-polarized (3)He gas is demonstrated in an open-access very-low-magnetic-field (<5 mT) MRI instrument. This prototype device employs a simple, low-cost electromagnet, with an open geometry that allows variation of the orientation of the imaging subject in a two-dimensional plane. As a demonstration, two-dimensional lung images were acquired with 4-mm in-plane resolution from a subject in two orientations: lying supine and sitting in a vertical position with one arm raised. Experience with this prototype device will guide optimization of a second-generation very-low-field imager to enable studies of human pulmonary physiology as a function of subject orientation.


Subject(s)
Helium , Isotopes , Lung/anatomy & histology , Magnetic Resonance Imaging/instrumentation , Administration, Inhalation , Equipment Design , Humans , Male , Middle Aged , Posture
19.
Phys Rev E Stat Nonlin Soft Matter Phys ; 70(2 Pt 2): 026312, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15447593

ABSTRACT

We report simultaneous measurements of the permeability and effective porosity of oil-reservoir rock cores using one-dimensional NMR imaging of the penetrating flow of laser-polarized xenon gas. The permeability result agrees well with industry standard techniques, whereas effective porosity is not easily determined by other methods. This NMR technique may have applications to the characterization of fluid flow in a wide variety of porous and granular media.

20.
Phys Rev E Stat Nonlin Soft Matter Phys ; 69(4 Pt 1): 041302, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15169012

ABSTRACT

A three-dimensional granular system fluidized by vertical container vibrations was studied using pulsed field gradient NMR coupled with one-dimensional magnetic resonance imaging. The system consisted of mustard seeds vibrated vertically at 50 Hz, and the number of layers N(l)

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