Computational study of haemodynamic effects of entry- and exit-tear coverage in a DeBakey type III aortic dissection: technical report.

OBJECTIVES: Outcome prediction in DeBakey Type III aortic dissections (ADs) remains challenging. Large variations in AD morphology, physiology and treatment exist. Here, we investigate if computational fluid dynamics (CFD) can provide an initial understanding of pressure changes in an AD computational model when covering entry and exit tears and removing the intra-arterial septum (IS). DESIGN: A computational mesh was constructed from magnetic resonance images from one patient (one entrance and one exit tear) and CFD simulations performed (scenario #1). Additional meshes were derived by virtually (1) covering the exit tear (false lumen (FL) thrombus progression) (scenario #2), (2) covering the entrance tear (thoracic endovascular treatment, TEVAR) (scenario #3) and (3) completely removing the IS (fenestration) (scenario #4). Changes in flow patterns and pressures were quantified relative to the initial mesh. RESULTS: Systolic pressures increased for #2 (300 Pa increase) with largest inter-luminal differences distally (2500 Pa). In #3, false lumen pressure decreased essentially to zero. In #4, systolic pressure in combined lumen reduced from 2400 to 800 Pa. CONCLUSIONS: CFD results from computational models of a DeBakey type III AD representing separate coverage of entrance and exit tears correlated with clinical experience. The reported results present a preliminary look at a complex clinical problem.

[Evaluation with chest CT scan of CPAP as a treatment for tracheobronchomalacia in the frame of a Mounier-Kuhn syndrome]. / Évaluation par tomodensitométrie thoracique d'un traitement de la trachéobronchomalacie par pression positive continue dans le cadre d'un syndrome de Mounier­Kuhn.

INTRODUCTION: Tracheobronchomegaly disease is often associated with a tracheobronchomalacia which is responsible for recurrent lower respiratory tract infections. Currently there is no evidence to support any specific treatment for the condition. CASE REPORT: We report the case of a 79 years old patient presenting with tracheobronchomegaly in the context of Mounier-Kuhn syndrome complicated by a tracheobronchomalacia responsible for her symptomatology. The diagnosis of tracheobronchomalacia had been confirmed by high-resolution chest computed tomography (CT) with expiratory slices and virtual bronchoscopy. Treatment with continuous positive airway pressure (CPAP) was proposed, and we confirmed its efficacy using high-resolution chest CT, which showed a decrease in tracheobronchial collapse and a reduction in air trapping. CONCLUSIONS: Three-dimensional virtual bronchoscopy is an interesting tool and a noninvasive method to diagnose tracheobronchomegaly for patients who are at a high anesthetic risk. It is also possible to use it demonstrate the effect of CPAP in tracheobronchomalacia.

[An analytical classification of fractures of the distal radius: The "M.E.U." classification]. / Classification analytique des fractures de l'extrémité distale du radius : la classification << M.E.U. >>

INTRODUCTION: Fractures of the distal radius are often complex injuries involving to a varying degree the radial metaphysis (M), radial epiphysis (E) and distal ulna (U). The association of these three parameters varies in a given injury and each fracture is a specific lesion which often defies inclusion in a well-defined group. An analytical classification is proposed. MATERIALS AND METHODS: The classification system analysed the three components of the fracture, assigning to each an index of gravity increasing from 0 to 4 and taking into account the main prognostic factor. Interobserver and intraobserver evaluation was carried out. The system was a posteriori applied to a prospective series of 166 distal radius fractures. RESULTS: Mean interobserver reliability was 0.78 and mean intraobserver reproducibility 0.81. M and E were closely correlated with treatment, M with algodystrophy, E with pain and U with mobility and patient satisfaction at one year. CONCLUSIONS: Inter- and intraobserver reproducibilities were good and the results validated our gravity indexes. This classification, describing all possible combinations of the three components of the fracture, is useful for both prognosis and treatment.

[Pre- and postoperative imaging of type B aortic dissection]. / Imagerie de la dissection aortique de type B : ce que veut savoir le chirurgien avant et après l'intervention.

Type B aortic dissections are serious diseases with a 60 to 80 % 5-year survival rate. Although typically managed with a medical treatment, surgery may be necessary in the acute/subacute or the chronic phase if significant complications are encountered. For these patients, CT angiography is the first-line imaging modality, used for indicating and preparing the surgical procedure as well as for follow-up. Physicians in charge of these patients should be familiar with the key reading points. Visceral malperfusion is the most common acute complication, while aneurysmal dilatation of the false lumen is the most common chronic complication, with surgical management generally indicated when the axial diameter of the aorta exceeds 55mm. Endovascular treatment tends to replace open surgery: it requires precise measurements and identification of the entry tear (contribution of 4D-MRA).

Triiodothyronine nuclear receptor and the role of non-histone protein factors in in vitro triiodothyronine binding.

The rat liver triiodothyronine (T3) nuclear receptor rapidly looses, after a partial purification from the nuclear extract, its ability to bind T3. We previously reported that histones, in the presence of DNA, could protect against inactivation enhancing the T3 binding site concentration and maintaining the high affinity for T3. A nuclear fraction discarded during the receptor purification (fraction A) was also found able to restore T3 binding and was analyzed. As histones + DNA, fraction A stabilized the T3 binding site from irreversible inactivation during incubation with T3, increasing its concentration while keeping the same high affinity for T3. It was active even at relatively high receptor concentration, appeared slightly more active than histones (+ DNA) in the same protein concentration range (up to 50-fold increment of T3 binding at the optimal concentration of 25 micrograms/ml) and was unaffected or slightly inhibited by DNA. Other proteins (ovalbumin, soybean trypsin inhibitor, RNAase) and rat liver cytosol were several times less effective, suggesting a major role of some nuclear constituents. The active factors in fraction A essentially belong to non-histone nuclear proteins. Fraction A was found heterogeneous regarding the molecular size and pHi of the active factors, the existence of subfractions more active on a protein concentration basis being suggested but not yet clearly evidenced. Efficient in vitro T3 binding to the isolated T3 nuclear receptor thus depends on the presence of several different nuclear constituents, histones + DNA or some non-histone proteins. Whether interactions with these constituents could modulate T3 binding within the nucleus remains to be elucidated.

Triiodothyronine nuclear receptor. Role of histones and DNA in hormone binding.

The triiodothyronine (T3) nuclear receptor was previously shown to lose rapidly its high affinity hormone-binding property after a partial purification from the nuclear extract. It was then found that histones + DNA added to the incubation medium with labeled T3 could restore, at least in part, the high affinity T3 binding. We now demonstrate that DNA alone increases the high affinity T3 binding site concentration moderately, and only at low ionic strength where it can bind to the receptor. Total histones and all histone fractions studied (total core histones, F2a, H2B, H3, H4, H1) specifically increase, at low concentrations, the level of T3 binding; but higher concentrations of some individualized histones, particularly arginine-rich histones, have an inhibitory effect. DNA, or several other polynucleotides, in the presence of histones increase the stimulating histone effect and reverse the inhibitory effect into a true activation. Histones increase the number of T3 binding sites but decrease the affinity for T3; addition of DNA restores the high affinity for T3 and stabilizes the T3-receptor complexes. Thus, some of the histone molecules could play a role in the maintenance of the T3 binding site, but multiple interactions between histones or with DNA seem necessary to impair the negative effect exerted by other parts of the histone molecules. Whether these positive and negative effects of histones on the T3 binding site are of biological relevance in the regulation of T3 binding to its receptor remains to be determined.

Increase of adipose differentiation by hypolipidemic fibrate drugs in Ob 17 preadipocytes: requirement for thyroid hormones.

The action of hypolipidemic fibrate drugs (HFD) (clofibrate, bezafibrate, fenofibrate) was studied in relation to thyroid hormone (TH) action in the TH-sensitive Ob 17 preadipocyte cells which require an early presence of TH for terminal differentiation. HFD markedly amplified the adipose differentiation and the development of several lipogenic enzymes, thus accelerating their appearance after cell growth arrest. This amplifying action could be obtained whatever the time of drug addition to the cells and required the continuous presence of the drug. HFD action was strictly dependent on the presence of TH. Within the active concentration range (0.01-0.25 mM) in serum-containing medium, HFD moderately down-modulated the nuclear TH receptor level (and c-erb alpha mRNA abundance), this being additive to the known maximal but partial down-regulation provoked by TH. The results strengthen the TH obligatory role for Ob 17 cell differentiation and give arguments against a TH-like role of HFD. In this cell line, HFD mainly behave as amplifiers for the expression of lipogenic phenotypes in already committed cells.

The effect of triiodothyronine on fatty acid synthetase activity and content in differentiating ob17 preadipocytes.

The effect of triiodothyronine on the activity and amount of the key lipogenic enzyme fatty acid synthetase was studied in differentiating preadipocyte cells (ob17) isolated from ob/ob mouse epididymal fat pad. In the presence of physiological concentrations of insulin, the acquisition of adipose morphology was accompanied by a parallel increase (10--15-fold) in synthetase specific activity and radioimmunoassayable amount relative to soluble cellular proteins. Inclusion of T3 at confluence significantly enhanced synthetase activity and content, with a maximum of 1.5--2-fold above controls at the physiological 1.5 nM concentration, whether insulin is present or not. During adipose conversion, T3 increased the development of enzyme activity and after a longer lag period, the accumulation of the synthetase. Our results suggest that the stimulating effect of T3 upon synthetase activity could involve as a first step the activation of preexisting inactive synthetase molecules and as a second one an increased accumulation of activable synthetase. After longer culture periods, inactive radioimmunoassayable synthetase accumulated.

Triiodothyronine (T3)-induced down-regulation of the nuclear T3 receptor in mouse preadipocyte cell lines.

As previously reported, preadipocytes cloned from the epididymal fat of lean or genetically obese mice (HGFu and ob 17, respectively) contain the nuclear T3 receptor. The number of receptor sites was similar in confluent cells of both lines and approximately doubled during adipocyte differentiation. T3 added to the culture medium increased triacylglycerol synthesis. T3 also increased fatty acid synthase specific activity, relative synthesis rate, and relative mRNA content (1.5- to 2.5-fold). Optimal responses were obtained at 1.5 nM. This study shows that under the same culture conditions in both cell lines, 1.5 nM T3 decreased the receptor concentration with no significant change in the affinity for T3. The receptor depletion was time dependent, rapid, stable in the presence of T3, and reversible in less than 24 h after its withdrawal. Receptor depletion was also dependent on T3 concentration and close to maximum at 1.5 nM T3 [45.1 +/- 2.7% (+/- SE) of the data values without T3; n = 14]. A linear relationship was observed between receptor occupancy by T3 and receptor loss. T4 and triiodothyroacetic acid also decreased the T3 receptor content, as expected from their own affinity for the receptor. These last two observations suggest that the receptor reduction is related to its occupancy by T3. The reported results, also observed in several other cell types, indicate that down-regulation of the nuclear T3 receptor by thyroid hormones is probably a generalized event in T3 target cells at least in vitro. Interpretation of its significance in preadipocyte cell lines requires further studies of rapid nuclear events following T3 receptor occupancy.

Retinoic acid decreases nuclear triiodothyronine receptor expression and impairs an early step of adipose differentiation in the thyroid hormone-sensitive mouse Ob 17 preadipocyte cell line.

In the murine preadipocyte cell line Ob 17, T3 is known to be necessary at an early step of adipose differentiation for the expression of late phenotypes [lipogenic enzymes such as malic enzyme, glycerol-3-phosphate dehydrogenase (GPDH), etc.] and not necessary for the expression of lipoprotein lipase (LPL), which emerges earlier, at growth arrest. These cells contain nuclear T3 receptors, which mainly belong to products of the c-erbA alpha gene and are down-regulated by T3. In this work, retinoic acid (RA) added to Ob 17 cells at growth arrest impaired morphological differentiation and the development of both late (malic enzyme and GPDH) and early (LPL) phenotypes regardless of whether T3 was added. T3 sensitized the cells to the inhibitory action of RA; the ED50 for GPDH activity was shifted from 0.5 microM to 3 nM in cells cultured with 1.5 nM T3. Later addition of RA (6 days after growth arrest) did not inhibit the differentiation. RA also brought out a marked and fast decrease in nuclear T3 receptors. This was observed whatever the stage of cell development and related to both a rapid decrease in the relative abundance of c-erbA alpha-related mRNA species and an increased disappearance rate, suggesting the involvement of pre- and posttranslational events. RA and T3 acted additively in decreasing the T3 receptor and c-erbA alpha mRNA levels. The effects of RA on T3 receptors were rapidly reversed after RA withdrawal; the reversal was large (75%) when RA was introduced at growth arrest and total when introduced later. The cell sensitivity to RA, considering the T3 receptors, was higher at growth arrest (ED50 for RA, 0.2 and 1.5 microM in assays with RA added at growth arrest and 5 days later, respectively). The results suggest intricated regulatory pathways between RA and T3 at an early step of adipose differentiation and also suggest that among different mechanisms through which RA may impair this differentiation, a decreased level of nuclear T3 receptors at an early period should play a role.

Heterogeneous distribution of nuclear triiodothyronine receptors in liver and preadipose cells as evidenced by their reactivity to antibodies against different protein products of erb A oncogenes.

Polyclonal antibodies raised in rabbits against bacterially produced peptides in the C-terminal region of v-erb A or human c-erb A alpha oncogenes recognize the nuclear triiodothyronine (T3) receptors in the T3-sensitive Ob 17 mouse preadipocyte cell line and not in mouse or rat liver. The results confirm the existence of different T3 receptors in different tissues. The results also suggest a heterogeneous receptor distribution within the preadipose cell line, with a predominance of c-erb A alpha-type species. Antibodies raised against domain 149 227, but not against domain 245-325, impair T3 binding, suggesting a role for this domain in ligand binding.

Antibodies against restricted sequences in human c-ErbA hinge domain recognize differentially natural mammalian alpha- or beta-type triiodothyronine receptors and interfere differently with hormone binding.

In our first report, rabbit antibodies directed to recombinant polypeptides of human alpha-type c-ErbA sequences recognized natural triiodothyronine (T3) receptors (TR) in adipocytes (mouse Ob 17 cell line) but not in liver (mouse, rat). Moreover, some of them, directed to the sequence 150-228, markedly interfered with hormone binding to adipocyte T3 receptors. We now raised antibodies against shorter synthetic peptides within this alpha-type 150-228 c-ErbA sequence, which encompasses part of the hinge (D) domain and N-terminus of the E domain (alpha-150-166 and alpha 172-191) and against a beta-type c-ErbA sequence (beta 204-220 aligned on alpha 150-166, and differing by eight amino acids). Our present antibodies, which bear the expected c-ErbA alpha- or beta-type specificity, immunoprecipitated the TR in nuclear extracts, with a different pattern between tissues: exclusive precipitation by anti-c-ErbA alpha antibodies in Ob 17 adipocytes; large but non-exclusive precipitation by anti-cErbA beta antibodies in rat or mouse liver, which also expresses some alpha-type TR. This pattern of discriminative immunoprecipitation, also obtained in parallel analysis using our previously described antibodies to other c-ErbA alpha or beta sequences (anti-alpha 144-162, anti-alpha 1 403-410 and anti-beta 62-82), roughly verifies results of c-erbA mRNA expression in these tissues. Slight differences appeared in the extent of alpha-type TR recognition by antibodies directed to alpha 172-191, whether TR were liganded or not to T3 before antibody addition. This evokes a different conformation of this region after hormone binding. Most interestingly, these anti-alpha 172-191 antibodies lowered the Ka for T3 and extensively dissociated the adipocyte T3-TR complexes; they interfered poorly with the binding of T3 in liver nuclear extracts. This strongly supports the concept that internal sequences in c-ErbA alpha, more precisely in a restricted C-terminal part of the D domain, are necessary for efficient T3 binding, which also need the C-terminal part of domain E.

Binding of 3,5-diiodotyrosine to serum proteins.

The reversible binding of 3,5-diiodotyrosine (DIT) to human and bovine serum protein and to purified human serum prealbumin and human and bovine albumin has been studied by equilibrium dialysis. Maximum binding occurred at pH 8.6-9.0. Human serum bound DIT less than did bovine serum. Adult ox and fetal calf sera showed similar binding. The main DIT-binding protein of human serum was prealbumin. It showed a single affinity site with a Ka of 0.85 X 10(6) M-1 at pH 8.6 and 0.40 X 10(6) M-1 at pH 7.4. The affinity constant of serum albumin for DIT was 2.8 X 10(3) M-1 at pH 8.6. The elevated binding of DIT to bovine serum is essentially due to albumin whose affinity constant for DIT is 16-times higher than that of human serum albumin. Fetuin was not responsible for any noticeable DIT binding in fetal calf serum.

Real-time spatial compound imaging improves reproducibility in the evaluation of atherosclerotic carotid plaques.

Compound imaging has the ability of reducing speckle and clutter artifacts demonstrated in in vitro studies compared to conventional, single-angle imaging. We investigated intra- and interobserver agreement of 38 outlines of carotid artery plaque images acquired by these techniques, by measuring the overlapping area after repeated outlines. In general, both techniques showed good agreement. When considering the images with poorest overlap, compound imaging had a significant advantage over conventional imaging regarding both intra- and interobserver agreement. The interobserver variation for the overlapping area after two outlines was 20% for conventional technique and 10% for compound. The interobserver variation of the gray scale median value (GSM) for conventional technique ranged from -32 to +20 and from -6 to +6 for compound. Likewise, the coefficient of repeatability for the GSM value was 13 for conventional imaging and three for compound imaging, and interobserver variation for the GSM value for the overlapping area was 34% and 9% for conventional and compound technique. In conclusion, compound imaging improves intra- and interobserver agreement and reduces interobserver variation in the GSM value in a clinical setting.

Intraluminal calcification of the abdominal aorta.

A patient who had no evidence of atherosclerotic disease and had never been hypertensive, presented with symptoms usually associated with gallstone disease. A large intraluminal calcification in the juxtarenal aorta was found to be the probable cause of these symptoms. The aorta was otherwise free of atherosclerotic changes. Although it could not be identified with certainty, this calcification could have developed secondary to a single ulcerated atheroma.

[Retinoic acid reduces the expression of nuclear receptors of triiodothyronin and inhibits an early stage of the differentiation in the Ob 17 preadipocytic strains]. / L'acide rétinoïque diminue l'expression des récepteurs nucléaires de triiodothyronine et inhibe une étape précoce de la différenciation dans la lignée préadipocytaire Ob 17.

In the murine preadipocyte cell line Ob 17, T3 is known as being necessary at an early step of adipose differentiation for the expression of late markers, but not necessary for the expression of early markers. These cells contain nuclear T3 receptors (RT3) which are products of c-erb A alpha proto oncogenes, and are down-regulated by T3. In these cells, retinoic acid (AR) inhibits the adipose differentiation and the expression of early and late markers, and T3 sensitizes the cells to the inhibitory action of AR. We also show that AR down-regulates the expression of RT3 at both pre- and post-translational levels. This inhibition is dependent on AR concentration, a peculiar sensitivity to AR being observed at an early step of development.

Intracarpal ligamentous lesions associated with fractures of the distal radius: outcome at one year. A prospective study of 95 cases.

Intracarpal ligamentous lesions associated with fractures of the distal radius (FDR) are frequent. The prevalence of these lesions has been assessed either by arthrography or by arthroscopy, but their outcome remains unknown. We carried out a radiographic study to assess the incidence of intracarpal ligamentous lesions with scapholunate (SL) and/or lunotriquetral (LT) dissociation and their outcome at one year. These lesions were termed "dissociative ligamentous lesions" (DLL). This prospective series consisted of 102 consecutive FDR's. The initial x-rays, immediate postoperative x-rays and x-rays at 1 year were studied. We studied the relationships of the bones of the first carpal row, abnormal joint space widening, Gilula's lines and the values of the intracarpal angles. The evolution of the carpal height ratio between day 0 and one year was studied. Complete xrays were available for 95 patients. There were 9 epiphyseal, 45 metaphyseal and 41 mixed fractures. DLL's were diagnosed in the early stages in 40 patients. There were 29 isolated SL lesions, 2 isolated LT lesions and 9 cases of associated SL and LT lesions. At 1 year, the diagnosis was confirmed in all these cases but a further case of SL dissociation was diagnosed. At 1 year, 61% of DLL's showed significant loss of carpal height and were considered as progressive. There was an association between the type of fracture and the presence or absence of DLL (p = 0.02). This study, based on radiographic analysis alone, showed 43% DLL's. The majority could be identified immediately. These findings are similar to those in recent arthrographic or arthroscopic studies, but the interest of plain radiographic study is to diagnose only those lesions having a definite effect on the carpus ("static instability"). At 1 year, 61% of lesions diagnosed have significantly affected carpal height.

[Thyreotoxic periodic paralysis. A cause of pseudo-paralysing hypokalemia that should not be ignored in Caucasians]. / Paralysie périodique thyréotoxique. Une cause d'hypokaliémie pseudoparalysante à ne pas méconnaître chez le Caucasien.

INTRODUCTION: Despite its rare occurrence in Caucasians, thyreotoxic periodic paralysis should be evoked in young male Caucasians presenting with episodes of pseudo-paralytic hypokalemia. OBSERVATION: A 37 year-old Caucasian was admitted in intensive care for an acute episode of hypotonic tetraplegia and hypokalemia during which laboratory tests revealed hyperthyroidism due to Basedow's disease. The clinical course was rapidly favourable after a small dose of intravenous potassium. Antithyroid treatment avoided any new occurrence of similar episodes. DISCUSSION: In Caucasians, sporadic acute paralysis with hypokalemia requires testing for hyperthyroidism. Though it is well know that hypokalemia results from potassium intracellular shift, the underlying mechanism remains poorly elucidated. Treatment includes potassium administration with caution and/or beta blockers but the specific treatment is that of hyperthyroidism.

[Lipid lowering treatment of patients with atherosclerotic disease of the lower extremities]. / Lipidsaenkende behandling af patienter med aterosklerotisk sygdom i underekstremiteterne.

Patients with critical peripheral ischaemia have a significant mortality rate of up to 50% within 4-5 years of surgical vascular reconstruction. This poor survival rate is due to concomitant coronary and cerebrovascular atherosclerotic disease. Large randomised trials have shown that dyslipidaemia is easily modifiable in patients both with and without established coronary artery disease, with significant reductions in cardiovascular morbidity and mortality. Although none of these trials directly measured peripheral vascular status, there is every indication that conclusions submitted for patients with ischaemic heart disease can be translated to patients with peripheral arterial disease (PAD). The object of this review was therefore to divulge the current evidence available, which supports active treatment of dyslipidaemia in patients with PAD.

[Amiodarone: a new cause of hypersensitivity pneumopathy?]. / L'amiodarone: une nouvelle cause de pneumopathie par hypersensibilité?

A 69 year-old woman with no previous history of lung disease was treated with 500 mg of Amiodarone per week. After 21 months of treatment, she developed a clinical picture of alveolitis with fibrosis, which was confirmed by histological examination. No other drug known for its fibrotic properties had been administered. Treatment with Nifedipine and Isosorbide dinitrate had been prescribed prior to the Amiodarone. Simply stopping the Amiodarone led to a regression or disappearance of the clinical, radiological and functional signs. Immunological investigations revealed the presence of antinuclear antibodies and a positive lymphoblastic transformation test for the drug, which are the abnormalities that one finds in other types of drug-induced fibrosis (nitrofuradantin). A new finding was the presence of cutaneous immunofluorescence of granular deposits of IgG, IgM and complement at the dermo-epidermal junction. So far, there have been 13 cases of lung disease related to the administration of Amiodarone reported in the literature.