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.

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.

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.

Effect of 4-hydroperoxycyclophosphamide on leukemic and normal human myeloid progenitor cells.

The sensitivity of myeloid progenitor cells from normal subjects (N-CFU-GM) and from leukemic patients in complete remission (LR-CFU-GM) to 4-hydroperoxycyclophosphamide (4-HC) were compared to the sensitivity of leukemic progenitor cells (L-CFU) to this drug. The results were expressed as the dose of 4-HC needed to kill 90% (TD 90) of the progenitor cells. The mean TD 90 were respectively for N-CFU-GM : 59 (+/- 11 S.E.M.) nM ml-1 and for L-CFU 79 (+/- 6 S.E.M.) nM ml-1. Thus, L-CFU were equally sensitive to 4-HC as N-CFU-GM. Moreover, the mean TD 90 for LR-CFU-GM was 87 (+/- 5 S.E.M.) nM ml-1. Thus, the sensitivity of N-CFU-GM and LR-CFU-GM did not differ significantly from that of L-CFU. These results are not encouraging for the use of 4-HC in vitro to eliminate the residual leukemic cells from autologous bone marrow of AML patients in complete remission. The sensitivity of L-CFU was modified neither by previous cytoreductive therapy (different from cyclophosphamide) nor by the time elapsed since diagnosis of AML.

Does flow character of cardiopulmonary bypass make a difference?

The influence of pulsatile bypass flow on the performance of the cardiovascular system, fluids and blood balance, acid-base equilibrium, and splanchnic function was investigated. One hundred patients scheduled for elective coronary artery bypass grafting were randomly divided into a group of standard perfusion (NP) and a group of pulsatile perfusion (PP). At the end of the operation, similar cardiac performance developed in both groups that was higher than before bypass: left ventricular stroke work index after bypass, 56.8 +/- 2.7 gm/beat per square meter in the NP group and 56.7 +/- 2.6 gm/beat per square meter in the PP group (not significant). Further determinations did not differ among the groups. After discontinuation of cardiopulmonary bypass, bypass grafts flow measured using an electromagnetic probe did not differ among the groups. During the postbypass period, mean arterial pressure and systemic vascular resistance were similar (mean arterial pressure 86.8 +/- 1.6 mm Hg in the NP group and 88.5 +/- 1.7 in the PP group; systemic vascular resistance 817 +/- 33 dyne.sec/cm5 in the NP group and 881 +/- 34.5 in the PP group), as were further determinations. However, severe hypotension requiring the administration of vasoconstrictors was observed more frequently in PP group of patients (20 versus 6%; p < 0.05). Fluid balance determined at the second postoperative day was similar among the groups (+1307 +/- 239 ml in the NP group and +1535 +/- 266 ml in the PP group). Blood loss was 1122 +/- 120 ml in the NP group and 1263 +/- 119 ml in the PP group during the first postoperative day (p = 0.407). Urine output during bypass was lower in the PP group (261 +/- 25 versus 341 +/- 26 ml/hr; p = 0.028). The creatinine clearance was 96.4 +/- 10.3 ml/min in the NP group and 92.6 +/- 7.0 ml/min in the PP group (not significant); amylase and lipase clearance did not differ among the groups. Finally, no significant difference was detected in arterial lactic acid determinations and acid-base balance assessment between the groups postoperatively. Thus equivalent cardiovascular hemodynamics, a good control of fluids and blood balance, acid-base equilibrium, and a satisfactory protection of the function of kidneys and pancreas were obtained with both types of perfusion.

Lactoferrin: its role as a regulator of human granulopoiesis?

Lactoferrin has been proposed recently as a physiological regulator of the granulocyte-monocyte progenitor (CFU-GM). This glycoprotein, when saturated with iron, has been said to limit the CFU-GM growth by decreasing production and release of colony stimulating activity by monocytes and macrophages. Human milk lactoferrin saturated with iron, at concentrations ranging from 10(-8) M, was added either to endogenously stimulated bone marrow cells or to mononucleated cells used as feeder layers for adherent cell-depleted marrow. Irrespective of the concentration of lactoferrin within the culture system used, no significant inhibition of the CFU-GM growth was observed. Moreover, the CFU-GM stimulating activity of medium conditioned by a 4 day incubation of 1 X 10(6) mononucleated blood cells in the presence or in the absence of lactoferrin was the same. Various possible explanations for not confirming the reported inhibiting activity of iron-saturated lactoferrin were explored: (a) masking inhibition of the system by prostaglandin E2 (PGE2), (b) masking inhibition of the system by bovine lactoferrin present in the fetal calf serum, (c) preinhibition of the system by leukemic-associated inhibitory activity possibly present in the culture system, (d) the iron and calcium content of the culture medium used, (e) the fixation of lactoferrin to plastic compounds, (f) the source of the human lactoferrin used, and (g) the marrow cell separation methods used. None of these factors was shown to play a role in vitro in the activity of lactoferrin and thus no evidence was found for a significant role of lactoferrin in the regulation of human granulopoiesis.

Operation for unstable angina pectoris: factors influencing adverse in-hospital outcome.

Coronary artery bypass grafting for the treatment of unstable angina is still associated with increased operative risk and postoperative morbidity. The impact of the extended use of arterial grafts on early results is incompletely defined. In a 7-year period (1986 to 1993), 474 patients (average age, 65 years; range, 34 to 85 years) underwent coronary artery bypass grafting for the treatment of unstable angina. Sixty-eight patients were operated on emergently and 406 urgently. They received an average of 3.0 distal anastomoses (range, 1 to 6). Seventy-nine patients had exclusively venous grafts, 316 had one internal thoracic artery graft, 79 had bilateral internal thoracic artery grafts, and 20 had inferior epigastric artery grafts. Sequential internal thoracic artery grafting was performed in 70 patients. Redo operations were performed in 26 patients. Thirty-four patients (7.2%) experienced a new myocardial infarction. Eighty-nine patients (18.8%) had an intraaortic balloon pump inserted preoperatively, intraoperatively, or postoperatively. Eight patients (1.7%) died intraoperatively and 24 patients (5.1%) died postoperatively. Seventy-seven patients (16.2%) had an adverse outcome, as shown by the need for an intraaortic balloon pump (intraoperatively or postoperatively) or hospital death, or by both. Forty variables were examined by multivariate analysis for their influence on the occurrence of an adverse outcome. Aortic cross-clamp time (p = 0.0004), transfer from the intensive care unit (p = 0.0023), female sex (p = 0.0023), operation performed in early years (p = 0.0041), left ventricular aneurysm (p = 0.0068), the number of diseased coronary vessels (p = 0.0312), and reoperation (p = 0.0318) were all found to be significant independent predictors of increased risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial experience with low-potassium cold blood cardioplegia: a clinical comparative study.

This study presents the results of bypass grafting in 96 patients operated on for triple-vessel coronary artery disease between May 1988 and September 1990. In the first 54 patients a cold crystalloid solution was employed, and in the 42 more recent patients cold blood low-potassium cardioplegia was employed. There were no differences in postoperative cardiac index or left ventricular stroke work index. Yet, in patients with impaired prebypass left ventricular stroke work index, postbypass left ventricular performance correlated negatively with duration of aortic cross-clamping in the cold crystalloid group (r = -0.441, p = 0.045). In contrast, no correlation was found in the cold blood low-potassium group (r = 0.125, p = 0.587). The incidence of myocardial infarction, need for inotropic support, and need for intraaortic balloon counterpulsation were similar among the groups. Release of the myocardial isoenzyme creatine kinase-MB from 12 to 30 hours after operation was significantly less in the low-potassium blood cardioplegia group. The use of low-potassium blood cardioplegia resulted in a marked reduction in the operative administration of fluids (1,527 +/- 87 versus 3,511 +/- 148 mL; p less than 0.001). In conclusion, low-potassium cold blood cardioplegia is a simple and effective method of myocardial protection. The fact that left ventricular stroke work index recovery was not dependent on the duration of aortic occlusion and that release of the MB isoenzyme of creatine kinase was reduced in the low-potassium blood cardioplegia group implies better myocardial protection.

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.

Diagnosis and treatment of pulpal distress.

Both diagnosis and treatment of vital pulp tissues encompass some fairly comprehensive varieties of methods and materials. Diagnosis is arrived at in terms of probability. No one can be absolutely sure that the diagnosed degree of pulpal distress is in fact the actual state of affairs. Treatment, therefore, must be best be a probability also. There can be no guarantee that the treatment rendered will succeed in every instance. Any diagnosis and treatment of reversible pulpal distress is a gamble on the part of both practitioner and patient. However, utilization of every diagnostic means at his disposal, knowledge of the many treatment modalities available for use, and the ability to correlate both the diagnosis and treatment phases of a given case will result in a high probability of success. This is indeed rewarding to both the patient and the dentist.

Pulmonary edema following acute upper airway obstruction.

During recovery, our patient presented an acute upper airway occlusion. After the removal of the airway obstruction, he developed a massive bilateral pulmonary edema with an acute hypoxemia. Hemodynamic measures following this incident show that mean and wedged pulmonary pressures are in the normal ranges. Several cases, associating acute upper airway obstruction, massive bilateral pulmonary edema and low or normal filling pressures, have been reported in literature. Three mechanisms have been postulated to explain this phenomenon; a dramatic increase of the negativity of the interstitial pulmonary pressure, a significative augmentation of the after-load and the hypoxic pulmonary reflex vasoconstriction.

A new lormetazepam galenical formulation for sublingual premedication.

This study reports a double-blind evaluation of a new formulation of lormetazepam for sublingual administration, given as a premedicant in 48 female patients undergoing minor gynecological procedures. Both patient's and nurse's assessments for anxiety and sedation were recorded at different times. Anxiolysis and sedation were present 30 minutes after administration of the drug as reported by the patient with a peak effect at 45 minutes. Nurses reported significant differences in sedation only, but already present at 30 minutes after premedication. The memory test showed no persistent effect of the benzodiazepine one day after surgery.

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.

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.

Plasma atrial natriuretic factor and catecholamines before and during excision of pheochromocytoma.

We studied changes of atrial natriuretic factor (ANF) and catecholamines in three patients with pheochromocytoma occurring in the familial syndrome of multiple endocrine neoplasia type IIa. Previous studies have suggested a stimulating effect of catecholamines on ANF release. In pheochromocytoma, we observed normal basal ANF levels despite increased catecholamine secretion. In contrast, a rise in plasma ANF was observed when a hypertensive paroxysm occurred. Also during surgery, dissection of pheochromocytoma led to a rise in plasma ANF and catecholamines associated with an increase in blood pressure (in the 3 cases) and in pulmonary artery pressure (in 2 cases). We concluded that chronic elevation of basal catecholamines are without effect on plasma ANF but that manipulation of pheochromocytoma leads to a stimulation of ANF release, possibly mediated by either a direct effect of endogenously released catecholamines and/or an increase in atrial pressure.

[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.

[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.