Biomedical subjects
Publications and source records attributed to C Thery.
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In B cells, the non-classical human leukocyte antigens HLA-DO (DO) and HLA-DM (DM) are residents of lysosome-like organelles where they form tight complexes. DM catalyzes the removal of invariant chain-derived CLIP peptides from classical major histocompatibility complex (MHC) class II molecules, chaperones them until peptides are available for loading, and functions as a peptide editor. Here we show that DO preferentially promotes loading of MHC class II molecules that are dependent on the chaperone activity of DM, and influences editing in a positive way for some peptides and negatively for others. In acidic compartments, DO is engaged in DR-DM-DO complexes whose physiological relevance is indicated by the observation that at lysosomal pH DM-DO stabilizes empty class II molecules more efficiently than DM alone. Moreover, expression of DO in a melanoma cell line favors loading of high-stability peptides. Thus, DO appears to act as a co-chaperone of DM, thereby controlling the quality of antigenic peptides to be presented on the cell surface.
PURPOSE: To evaluate the resolution of acute central pulmonary embolism (PE). MATERIALS AND METHODS: Sixty-two patients with angiographic (n = 43) or spiral computed tomographic (CT; n = 19) diagnosis of acute central PE underwent spiral CT after a mean of 11 months. CT signs of unresolved acute or chronic PE at the level of the central pulmonary arteries were recorded. A scoring system enabled quantification of endoluminal abnormalities at the time of diagnosis and follow-up. RESULTS: At follow-up, 30 patients (group 1; 48%) had complete resolution of acute PE; 32 patients (group 2; 52%) showed endovascular abnormalities (mean follow-up in both groups, 10.5 months). Whereas clinical presentation, risk factors at diagnosis, and therapeutic modalities did not differ statistically significantly between the two groups, group 2 had more extensive acute PE at diagnosis than did group 1. In group 2, CT showed an incomplete resolution of acute PE in 24 patients (group 2a; 39%) and development of chronic PE in eight patients (group 2b; 13%). Six patients had exertional dyspnea (five group 2a patients and one group 2b patient); five patients had echocardiographically demonstrated pulmonary hypertension (all group 2a patients). CONCLUSION: Spiral CT enabled noninvasive detection of unresolved PE and of newly developed chronic PE.
Acute myocarditis due to toxoplasmosis infection has been previously reported, usually in patients suffering from immuno-depression. Cardiac involvement by toxoplasmosis is rare in subjects with a normal immunological status. The authors report the case of a 16-year-old patient without immuno-depression with acute myocarditis caused by toxoplasmosis simulating myocardial infarction.
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It is now well recognized that a disorder of left ventricular filling can be sufficient to account for congestive heart failure. Furthermore, evaluation of heart disease would not be complete if it did not include assessment of left ventricular filling, improvement of which probably ensures better control of the heart disease. An efficient and reliable tool for the study of diastolic function is therefore essential. The authors review the current state of knowledge and the more recent developments in Doppler echocardiography in the evaluation of left ventricular diastolic function. After revising the pathophysiology, the methods of studying ventricular filling are described. The recording technique is described, taking into account recent developments in transthoracic and transoesophageal approaches. This investigation provides parameters allowing semiquantitative estimation of filling pressures (mean left atrial pressure, end-diastolic pressure) and reliable evaluation of overall diastolic performance.
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We have used in situ hybridization to survey the expression pattern of three fibroblast growth factor receptor (FGFR) mRNAs (PFR-1, PFR-3 and PFR-4, which we previously identified as the amphibian Pleurodeles waltl homologs of human FGFR-1, FGFR-3 and FGFR-4, respectively) during morphogenesis. Previous work suggests that these FGFR mRNAs exhibit a distinct pattern of expression at early developmental stages. In the present study we have tested the functional activity of these receptors and shown that both FGF-1 (acidic FGF) and FGF-2 (basic FGF), but not FGF-7 (keratinocyte growth factor), can lead to their activation, suggesting that the three cDNAs encode functional receptors. Results from in situ hybridization indicate that various FGFRs are involved in various developmental events. Their involvement in these processes is both overlapping and distinct. During the differentiation of the central nervous system (CNS), PFR-1 and PFR-4 mRNAs show high levels of redundant expression, while the sites of expression of PFR-3 mRNA correlate with regions, such as the diencephalon and the rhombencephalon, undergoing important anatomic changes. The three FGFR mRNAs are distinctly expressed in the cranial ganglia, the pigmented epithelia of retina and the otic vesicles. Most significantly, we found that they are strongly expressed at cranial and branchial mesenchymal condensation sites. PFR-3 mRNA is expressed earlier in this process than PFR-1 and PFR-4 mRNAs. Furthermore PFR-3 mRNA is detected in the mesenchyme of the limb bud, while PFR-1 and PFR-4 mRNAs are found in the primordia of the skeletal elements. In addition, PFR-1 mRNA is expressed in axial mesenchyme and PFR-4 mRNA is detected in the melanophores, xanthophores and in the pronephros. These results suggest that various FGFRs may be involved in distinct developmental events including cell proliferation and differentiation. We also discuss the functional redundancy of the FGFR system during amphibian morphogenesis.
The authors report another case of rupture of the thoracic aorta in Giant Cell arteritis. The progressive nature of the rupture enabled life-saving aortic replacement with a vascular prosthesis. Only one previous report of this type of operation was found in a search of the literature. The prevalence of aortitis in Giant Cell arteritis would appear to be underestimated after autopsy studies. It affects the thoracic aorta mainly in the ascending segment but sometimes involves the whole aorta. It may remain asymptomatic or be complicated by arterial occlusion, aortic regurgitation, aneurysm, dissection or rupture. Effective steroid therapy could prevent these complications.
Systemic thrombolysis is less than optimal in total occlusions of the iliac vein in which patency is 20% or less. We describe an interventional therapeutic procedure that may be effective in such cases. We selected 18 patients (average age, 29.5 years; range, 16 to 71 years) with complete iliac vein occlusion that persisted after 24 to 48 hours of systemic thrombolysis (streptokinase 100,000 U/hr). The ipsilateral femoral vein was punctured, and a guide wire was gently advanced through the thrombus into the inferior vena cava. Multiple inflations were performed with a balloon catheter that was advanced on the wire. A temporary vena cava filter was placed as a protection against possible embolic migration. Systemic thrombolysis was administered for 24 to 48 hours. Control venography and pulmonary angiography were performed. Venography showed good recanalization in seven cases, incomplete recanalization in five cases, and failure in six cases. Patency was maintained for a long time (15.6 months). In conclusion, (1) percutaneous transluminal venous angioplasty is a valuable adjunct to systemic thrombolysis when the latter alone fails; (2) segmental flow and mechanical obstruction were the critical factors, since the pharmaceutical factors were held constant, and (3) a more aggressive incremental interventional strategy warrants consideration.
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Fifty patients (38 men) with unstable angina pectoris defined by: pain lasting > 15 minutes+percritical electrocardiographic changes+significant coronary narrowing on coronary angiography (Coro 1) performed within 24 hours, were treated in a double blind protocol with rt-PA (n = 25) 100 mg/90 minutes (10 mg bolus + 90 mg/90 minutes or placebo (n = 25). All received effective intravenous heparin and intravenous nitrates. Calcium antagonists and betablockers were prescribed in half the cases. Aspirin (100 mg orally per day) was prescribed after control coronary angiography (Coro 2) performed 24 +/- 6 hours after starting treatment. Qualitative and quantitative analysis (CAESAR system) was centralised. There were no differences in the angiographic findings between the two groups. Intracoronary thrombosis was observed in 43% (rt-PA) and 44% (placebo) in Coro 1 and in 17% and 28% in Coro 2. The incidence of myocardial revascularisation procedures was similar in the two groups: angioplasty: 12 (rt-PA) and 13 (placebo); coronary bypass surgery: 5 (rt-PA) and 6 (placebo). Seven patients developed myocardial infarction (5 rt-PA, 2 placebo), one of whom died of cardiogenic shock (placebo). Eighteen patients had haemorrhagic complications (14 rt-PA, 4 placebo; p < 0.002) mainly at the puncture sites (12/14, 3/4). Spontaneous haemorrhage occurred in 7/25 (28%) of patients on rt-PA (haematuria 3, gastrointestinal haemorrhage 2, haematuria + gastrointestinal haemorrhage 1, epistaxis 1) and in 1/25 patients on placebo (gastrointestinal haemorrhage) This study shows that intravenous thrombolysis with rt-PA in severe unstable angina pectoris doe not modify the clinical outcome or the angiographic lesions but exposes patients to a high risk of haemorrhagic complications.
Non-valvular atrial fibrillation multiplies the risk of presumed embolic events by a factor of four. The hemorrhagic risk of anticoagulant treatment varies considerably and its prophylactic efficacy was not tested in any randomised trial before the end of 1989. The recommendations of experts at that time recognised that data were inadequate. The publication since of four randomised trials involving 3,049 patients has provided a more objective base for management decisions, highly in favour of the anticoagulation of cases of non-isolated atrial fibrillation in the absence of contraindications.
The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering.
Ten patients with sick sinus syndrome having repetitive sinus node electrograms during long postpacing pauses were studied during programmed atrial stimulation. Sinus node activity was recorded using a percutaneous catheter electrode. A sinus node electrogram was recorded before the return atrial beat in seven patients; it was similar to the sinus node electrogram observed during postpacing pauses and is clearly identified because sinoatrial conduction time was markedly prolonged following the atrial extra beat. Complete sinoatrial exit block occurred in four patients. (1) Sinus node electrograms were thus validated both during postpacing pauses and during programmed atrial stimulation in most patients with sick sinus syndrome. (2) Sinoatrial conduction time was markedly prolonged after one extrasystole, accounting for supracompensatory atrial return cycles. (3) If it were cumulative following multiple extrasystoles, this effect could constitute the electrophysiologic link between an abnormal response during programmed atrial stimulation and the complete sinoatrial block recorded during the pauses that follow rapid atrial pacing.
The authors present a removable vena cava filter that may be introduced percutaneously, is atraumatic to the venous wall, and permits the simultaneous use of thrombolytic therapy. Sixty-five patients were studied: 42 cases of pulmonary embolism with threatening venous thrombosis; 23 cases of phlebitis associated with an ilio-caval thrombus without pulmonary embolism. The filter was introduced 38 times femorally and 27 times by a jugular approach. In 16 cases (24.6%) clots broke loose, were effectively caught by the filter, and were progressively dissolved during thrombolytic therapy. The filter remained in place on average 4.5 +/- 1.2 days. The filter was removed in all cases without provoking the recurrence of pulmonary embolism. Two deaths, not related to pulmonary embolism, occurred during hospitalization. Phlebography, performed in all cases before and after treatment, showed a significant decrease of the phlebographic score (10.88 +/- 0.82 vs 6.77 +/- 0.86, P less than 0.001). The same was observed in 40 patients who underwent a pulmonary angiography before and after treatment (Miller index = 17.04 +/- 0.73 vs 5.49 +/- 0.87, P less than 0.0001). After removal of the filter, no sign of pulmonary embolism was detected on lung scan in the 23 patients with ilio-caval thrombus alone. More than 5 g (100 ml)-1 of haemoglobin was lost by 15.38% of patients. All patients were followed-up for a mean of 7.12 +/- 1.3 months; in no case was there any clinical recurrence of pulmonary embolism. Thus this device allows an effective temporary filtering of the vena cava.(ABSTRACT TRUNCATED AT 250 WORDS)
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