Tandem inversion duplication within F8 Intron 1 associated with mild haemophilia A.

In approximately 90% of mild haemophilia A (HA) patients, a missense mutation can be identified using complete gene sequencing. In this study, multiplex ligation-dependent probe amplification analysis was performed as a second step in 10 French-speaking Belgian with mild HA presenting no detectable causal mutation by complete sequencing of the factor VIII (FVIII) (F8) gene's 26 exons and its 1.2 kb of contiguous promoter sequence. This gene dosage technique enabled the detection of exon 1 duplications of F8 in three apparently unrelated subjects. Using array-comparative genomic hybridization, breakpoint analysis delimited the duplication extent to 210 kb in the F8 intron 1 and VBP1 gene intragenic position. We postulated that the rearrangement responsible for this duplication, never before reported, could be attributed to a symmetrical tandem inversion duplication, resulting in a large 233 kb rearrangement of F8 intron 1. This rearranged intron should lead to the production of a small number of normal mRNA transcripts in relation to the mild HA phenotype. Our analysis of the entire F8 mRNA from index case 1, particularly the segment containing exons 1-9, revealed normal amplification and sequencing. Reduced plasma FVIII antigen levels caused by cross-reacting material is associated with a quantitative deficiency of plasma FVIII. Male patients were unresponsive to desmopressin (1-deamino-8-D-arginine vasopressin). All patients displayed identical F8 haplotypes, despite not being related, which suggests a possible founder effect caused by a 210 kb duplication involving F8 exon 1.

Anesthesia for adult rigid bronchoscopy.

Rigid bronchoscopy under general anesthesia enables performing diagnostic and/or therapeutic procedures in the tracheobronchial tree. This technique is characterized by specific technical problems, insofar as the anesthesiologist and the operators share the same space, namely the airway. Several potential complications (hemorrhage inside the airway, threat to ventilation ...) may arise. These challenges render the ability to use the variable available techniques essential, as well as knowledge of the complications they could entail, and the ability to rapidly solve them. General anesthesia is usually total intravenous anesthesia, using short acting agents. Ventilation can be spontaneous, but more often insured using high-frequency jet ventilation. The hospital infrastructure and staff must have the expertise to perform this particular procedure, in order to limit the complication rate.

[Prospective trial comparing Airtraq and Glidescope techniques for intubation of obese patients]. / Étude prospective comparant la technique de l'Airtraq et du Glidescope lors de l'intubation chez les patients obèses.

OBJECTIVES: Videolaryngoscope techniques are more and more in use and tend to modify our approach for patients difficult to intubate. We compared two techniques, Airtraq and Glidescope with direct laryngoscopy, with special emphasis on ease of access to airway (Intubation Difficulty Score - IDS score, duration and success of intubation) and the impact on hemodynamic variables among patients with a BMI of more than 30. STUDY DESIGN: Prospective study randomised with minimisation technique. MATERIAL AND METHODS: Eighty patients have been allocated by minimisation to four groups: two groups being intubated with Airtraq, each one with a different investigator, and two with Glidescope videolaryngoscope technique. Induction of anesthesia was standardly performed with total intravenous anesthesia with remifentanil, propofol in TCI mode and rocuronium in bolus. Following parameters were recorded : intubation success based on intubation time and desaturation level, its duration, its impact on hemodynamic variables, IDS score and possible dental lesions. RESULTS: Intubation success was 100% for Glidescope and 80.6% for Airtraq (P=0.009). Airtraq allowed a better visualisation of the vocal cords (lower Cormack and Lehane score) than Glidescope. In contrast, alternative intubation techniques were significantly more often used in the Airtraq group. No difference could be detected between both systems on hemodynamic parameters. CONCLUSIONS: In obese patients, Glidescope allows intubation relatively easily without rescue techniques.

Neonatal haemoglobinopathy screening in Belgium.

BACKGROUND: A neonatal haemoglobinopathy screening programme was implemented in Brussels more than a decade ago and in Liège 5 years ago; the programme was adapted to the local situation. METHODS: Neonatal screening for haemoglobinopathies was universal, performed using liquid cord blood and an isoelectric focusing technique. All samples with abnormalities underwent confirmatory testing. Major and minor haemoglobinopathies were reported. Affected children were referred to a specialist centre. A central database in which all screening results were stored was available and accessible to local care workers. A central clinical database to monitor follow-up is under construction. RESULTS: A total of 191,783 newborns were screened. One hundred and twenty-three (1:1559) newborns were diagnosed with sickle cell disease, seven (1:27,398) with beta thalassaemia major, five (1:38,357) with haemoglobin H disease, and seven (1:27,398) with haemoglobin C disease. All major haemoglobinopathies were confirmed, and follow-up of the infants was undertaken except for three infants who did not attend the first medical consultation despite all efforts. CONCLUSIONS: The universal neonatal screening programme was effective because no case of major haemoglobinopathy was identified after the neonatal period. The affected children received dedicated medical care from birth. The screening programme, and specifically the reporting of minor haemoglobinopathies, has been an excellent health education tool in Belgium for more than 12 years.

Case report: Severe laryngeal hemorrhage after withdrawal of a size 5 I-gel in elective surgery.

PURPOSE: Report a case of a patient, who benefitted from the I-gel, during an elective urological surgery and who presented severe laryngeal hemorrhage at the time of its withdrawal. CLINICAL FEATURES: A 71-year-old male patient had been admitted in the operating room for the insertion of a ureteral stent. He had a history of usual interstitial pneumonia (UIP) requiring corticosteroids and oxygen therapy and a severe obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure (NCPAP). After intravenous induction of anesthesia, a size 5 I-gel (Intersurgical, Wokhingam, UK) was easily inserted in the first attempt. Anesthesia was maintained with sevoflurane. As soon as the procedure ended, the I-Gel was removed. After two minutes, the patient presented a respiratory distress and started spitting significant quantity of blood. Oropharyngeal fiberscopy was performed in emergency and highlighted active bleeding of the left aryepiglottic fold. Hemostasis was obtained by local compression. The patient was transferred to the intensive care unit. He was extubated the following day without complications. No additional procedure was necessary to stop the bleeding. CONCLUSION: Authors reported the first severe complication associated with the use of size 5 I-gel. Additional studies have to be carried out to specify the advantages and risks associated with the use of this recent material.

[Paradox: when a prothrombotic disorder is responsible for an upper gastrointestinal bleeding. Case report of hepatoportal sclerosis]. / Paradoxe: lorsqu'un état prothrombotique est responsable d'une hémorragie digestive. Observation d'un cas de sclérose hépatoportale.

Variceal bleeding is frequently the initial presentation of a previously unknown cirrhosis. Portal hypertension and its complications without liver cirrhosis should raise the possibility of presinusoidal portal hypertension, and the diagnosis of hepatoportal sclerosis. These patients need to be investigated for coagulation disorders. A hypercoagulable state is often associated. Risks and benefits of anticoagulation should be further investigated in these patients.

Deletion of the 5'-ABL region: a recurrent anomaly detected by fluorescence in situ hybridization in about 10% of Philadelphia-positive chronic myeloid leukaemia patients.

Inclusion of the BCR-ABL ES probe in routine cytogenetics led to the identification of a subgroup of Philadelphia positive (Ph+) chronic myeloid leukaemia patients characterized by a 5'-ABL deletion. This anomaly was observed in 5/51 cases (9.8%). Cytological and clinical data suggest that the 5'-ABL deletion may be associated with dysplastic features of polymorphonuclear cells and metamyelocytes and a short chronic phase duration.

Evaluation of autoantibodies against oxidized LDL and antioxidant status in top soccer and basketball players after 4 months of competition.

Antioxidant status and titers of autoantibodies against oxidized low-density lipoproteins (ox-LDL-Ab) were investigated in top soccer (S; n = 21, age 24.6 +/- 4.3 years) and basketball (B; n 3,000 mIU/ml) in ox-LDL-Ab were found in half the players (12S and 4B) with a maximum reaching 6000 mIU/ml (normal range: 200-600 mIU/ml), showing an in vivo LDL oxidation. There was no correlation between ox-LDL-Ab titers and chlolesterol, LDL cholesterol, or antioxidant levels. Nevertheless, plasma vitamin C concentration was lower in athletes having high levels of ox-LDL-Ab when compared with those with normal levels (8.49 +/- 3.14 mirogram/ml vs. 10.39 +/- 2.55 microgram/ml), but this difference was not statistically significant. In conclusion, our data suggest that potential atherogenic and cardiovascular risks as reflected by high titers in ox-LDL-Ab may exist in some top athletes despite a nonaltered antioxidant status.

Doppler-derived left ventricular rate of pressure rise determination in presence of severe acute mitral regurgitation in pigs.

Doppler-derived left ventricular (LV) rate of pressure rise (Dop LV DeltaP/Deltat) is described as an index of LV performance in the presence of mitral regurgitation (MR). This study was designed to define more accurately the accuracy of the method in the presence of severe MR. Ten pigs were anesthetized and monitored. MR was gradually created. At each grade of MR, preload was manipulated with the intent of modifying LV end-diastolic area value within a range of +/-20%. Concurrently, the mean left atrial pressure (LAP) was recorded, MR was quantified by the mitral to aortic velocity-time integral ratio (mitroaortic VTI ratio), Dop LV DeltaP/Deltat was calculated, and peak LV dP/dt was derived from LV catheterism data. During the procedure Dop LV DeltaP/Deltat gradually underestimated peak LV dP/dt. This difference was correlated to the mean LAP (P < 10(-5)) and mitroaortic VTI ratio (P < 10(-5)) and became clinically significant when the mean LAP was superior to 21 mm Hg.

Patent foramen ovale and implantable cardioverter defibrillator.

A case of patent foramen ovale opening was observed concomitantly to a defibrillation threshold determination in the setting of an internal cardioverter defibrillator implantation. The subsequent transient right-to-left shunt was confirmed by a peroperative transoesophageal echocontrast study. The underlying mechanism of this incident may be related to a transient reversal of the interatrial gradient, due to the pre-existence of pulmonary hypertension and tricuspid regurgitation, associated with ongoing mechanical ventilation and modifications of intracardiac pressures regimen secondary to the succeeding ventricular tachyarrhythmia and defibrillation. Paradoxical embolism can be an aetiology for neurologic injury during internal cardioverter defibrillator implantation.

Laparoscopic adrenalectomy for phaeochromocytoma: endocrinological and surgical aspects of a new therapeutic approach.

OBJECTIVES: To evaluate the results of laparoscopic resection of phaeochromocytoma with a focus on pre- and intra-operative endocrinological and pharmacological aspects. DESIGN: Retrospective study based on review of case notes and intraoperative anaesthetic records. PATIENTS: Eight patients (four men, four women) aged 13 to 70 (median: 45) years with symptomatic phaeochromocytoma (two patients with MEN IIa syndrome) diagnosed 6-36 months before adrenalectomy in four patients and just before operation in the four remaining patients. All patients presented with hypertension. MEASUREMENTS: Pre- and postoperative blood pressure (BP) was assessed using a sphygmomanometer, intraoperative measurements being obtained by intra-arterial line. Adrenaline (A), noradrenaline (NA), metadrenaline (metA), normetadrenaline (normetA) and vanillylmandelic acid (VMA) were measured in 24-h urine samples. Adrenal imagery consisted in all patients of abdominal computed tomography and [131I] metaiodobenzylguanidine (MIBG) scintigraphy, and in 2 patients, adrenal magnetic resonance imaging and octreotide scintigraphy. Determination of plasma volume was performed by isotopic method. RESULTS: Median (range) preoperative systolic and diastolic BP was 140 (130-240) and 90 (80-150) mm Hg, respectively. Predominant catecholamine secretion consisted of A in four patients (A pattern) and of NA (NA pattern) in the other four. Tumours smaller than 30 mm usually secreted A while larger ones secreted NA. Pre- and intra-operative BP control was straightforward in all but two patients with preferential NA secretion. The median number of systolic and diastolic BP peaks were higher in patients with NA pattern (n = 6, range: 3-9) than in those with A pattern (n = 1.5, range: 1-6). Total duration of pneumoperitoneum ranged from 120 to 240 (median: 195) min. Intra- and post-operative complications included intra-abdominal bleeding, laparoscopically controlled (in one case), and upper pole kidney ischaemia in another. Postoperative hospital stay ranged from 4 to 11 days. All patients were asymptomatic postoperatively and pharmacologically controlled hypertension persisted in two of them. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and efficient technique to remove phaeochromocytoma in terms of intra- and postoperative morbidity, with a low complication rate. Pre- and intra-operative pharmacological blood pressure control is as effective as in conventional adrenalectomy, with greater instability in noradrenaline secreting tumours.

Doppler-derived left ventricular rate of pressure rise and inotropic requirements during mitral valve surgery.

BACKGROUND: The estimation of left ventricular (LV) contractility is difficult in the presence of significant mitral regurgitation (MR). Prediction of LV performance after MR repair is even more problematic. The intraoperative Doppler-derived LV rate of pressure rise (LV delta P/delta t) analyzed before cardiopulmonary bypass (CPB) was presumed to be a useful predictive parameter for LV performance. Therefore, its relation to perioperative inotropic requirements (PIR) necessary for separation from CPB after surgical MR repair was investigated. METHODS: Twenty-eight patients scheduled for surgical MR repair fulfilled the selection criteria. Pre-CPB LV delta P/delta t, pre-CPB echocardiographic LV fractional area change (LV FAC), and pre-CPB thermodilution-derived cardiac index (CI) were recorded. After MR repair, separation from CPB was performed with regard to standardized guidelines. PIR during the first 60 minutes following separation were recorded. RESULTS: Pre-CPB LV delta P/delta t could be assessed in 22 patients. Pre-CPB LV delta P/delta t was 882 +/- 450 mmHg/sec, pre-CPB LV FAC was 49% +/- 9%, and pre-CPB CI was 2.0 +/- 0.2 L/kg/min. Pre-CPB LV delta P/delta t was significantly correlated with pre-CPB LV FAC (r = 0.56), and with pre-CPB CI (r = 0.72). Inotropic support was necessary in 16 patients (73%), and was best predicted by the pre-CPB LV delta P/delta t, by means of logistic regression (p = 0.026). CONCLUSIONS: Doppler-derived LV delta P/delta t was assessable in most patients with severe chronic MR, and was the best intraoperative predictive parameter of post-CPB inotropic requirements after surgical MR repair.

Hemodynamic benefit of optimizing atrioventricular delay after cardiopulmonary bypass.

BACKGROUND: Shortening of atrioventricular delay (AVD) by sequential cardiac pacing has been proposed to improve hemodynamics in patients with end-stage heart failure. In addition, optimization of prolonged AVD may be associated with a decrease of presystolic mitral insufficiency. The aim of this study was to explore the incidence of prolonged AVD during the early postcardiopulmonary bypass (CPB) period and to evaluate the hemodynamic benefit of its shortening by using sequential cardiac pacing. METHODS: Fifty consecutive patients scheduled for coronary artery bypass grafting were prospectively screened. AVD was measured immediately after separation from CPB. Patients presenting with AVD greater than or equal to 200 ms entered the study. Sequential cardiac pacing was introduced with programmed AVD starting at 80 ms and randomly increased by steps of 20 ms until resumption of native anterograde atrioventricular node conduction. Cardiac index (CI) was derived from transesophageal echocardiographic data during each step of this procedure. RESULTS: Nineteen patients were included. Median native AVD was 220 ms. Median optimal AVD was 140 ms. Mean native CI (CI-nat) was 2.59 +/- 0.42 L/min/m2. Mean optimal CI (CI-opt) was 3.12 +/- 0.45 L/min/m2. CI-opt/CI-nat was 1.20 +/- 0.07. CI-opt/CI-nat was significantly inversely correlated with preoperative left ventricular ejection fraction (r = -0.83). CONCLUSIONS: Prolonged AVD is a common occurrence after CPB. Its artificial shortening by sequential cardiac pacing is always associated with a significant increase of CI. The magnitude of this hemodynamic improvement is inversely correlated with preoperative left ventricular ejection fraction.

Persistent left superior vena cava: transoesophageal echocardiographic findings and surgical strategies.

Two cases of casual discovery of persistent left superior vena cava during cardiac surgery are reported. Diagnoses were suspected at the time of peroperative transoesophageal echocardiography in the first case, and of preoperative fluoroscopy during a Swan-Ganz catheter insertion procedure in the second case. For both patients, a peroperative echo contrast study permitted to confirm the anomaly before initialization of cardiopulmonary bypass. Embryology, echocardiographic findings and surgical management, including cardioplegia delivering and left upper venous system drainage, are reviewed.