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Biomedical subjects

M Dahan

Publications and source records attributed to M Dahan.

At least 37 records · Page 2Linked to original sources

Ratiometric single-molecule studies of freely diffusing biomolecules.

We outline recent developments in biological single-molecule fluorescence detection with particular emphasis on observations by ratiometric fluorescence resonance energy transfer (FRET) of biomolecules freely diffusing in solution. Single-molecule-diffusion methodologies were developed to minimize perturbations introduced by interactions between molecules and surfaces. Confocal microscopy is used in combination with sensitive detectors to observe bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract ratiometric observables such as FRET efficiency and polarization anisotropy. We describe the development of single-molecule FRET methodology and its application to the observation of the Förster distance dependence and the study of protein folding and polymer physics problems. Finally, we discuss future advances in data acquisition and analysis techniques that can provide a more complete picture of the accessible molecular information.

Biopolymers↗

Rate of abnormal osteoarticular radiographic findings in pediatric patients.

OBJECTIVE: The objective of our study was to assess the rate of abnormal radiographic findings in the most frequent osteoarticular locations of traumatic injury in a pediatric population. SUBJECTS AND METHODS: During two periods of 12 weeks each, all patients admitted to the pediatric emergency department for osteoarticular trauma who underwent radiography were prospectively included in this study. A connection was drawn between the rate of abnormal radiographic findings for the seven most frequently radiographed locations and the clinical findings. RESULTS: Of 3128 locations of trauma in 2470 children, only 22% of the radiographic examinations were considered to reveal abnormal findings. In decreasing order, the hand and fingers, the ankle, the wrist, the knee, the elbow, the foot and toes, and the forearm were the most frequently examined locations. The rate of abnormal findings was 25.7% for the hand and fingers, 9.0% for the ankle, 42.5% for the wrist, 9.5% for the knee, 33.3% for the elbow, 18.3% for the foot, and 43.2% for the forearm. When only the direct sign of fracture was taken into account, these rates decreased for the ankle and knee to 2.6% and 1.9%, respectively. There was always a significant link between the degree of clinical suspicion and the rate of abnormal radiographic findings. However, fewer than 50% of the cases with high clinical suspicion of fracture were radiographically confirmed. CONCLUSION: It appears necessary, especially in cases of lower limb trauma, to evaluate clinical tests, including the implementation of the Ottawa ankle rules, to reduce the number of unnecessary radiographic examinations. This reduction will improve some parameters of children's quality of life and will significantly decrease the cost of emergency care.

Adolescent↗

Single-molecule protein folding: diffusion fluorescence resonance energy transfer studies of the denaturation of chymotrypsin inhibitor 2.

We report single-molecule folding studies of a small, single-domain protein, chymotrypsin inhibitor 2 (CI2). CI2 is an excellent model system for protein folding studies and has been extensively studied, both experimentally (at the ensemble level) and theoretically. Conformationally assisted ligation methodology was used to synthesize the proteins and site-specifically label them with donor and acceptor dyes. Folded and denatured subpopulations were observed by fluorescence resonance energy transfer (FRET) measurements on freely diffusing single protein molecules. Properties of these subpopulations were directly monitored as a function of guanidinium chloride concentration. It is shown that new information about different aspects of the protein folding reaction can be extracted from such subpopulation properties. Shifts in the mean transfer efficiencies are discussed, FRET efficiency distributions are translated into potentials, and denaturation curves are directly plotted from the areas of the FRET peaks. Changes in stability caused by mutation also are measured by comparing pseudo wild-type CI2 with a destabilized mutant (K17G). Current limitations and future possibilities and prospects for single-pair FRET protein folding investigations are discussed.

Energy Transfer↗

Intrathoracic migration of Kirschner pins.

We report two cases of intrathoracic migration of Kirschner pins used for the treatment of sternoclavicular joint dislocation. The migration was asymptomatic in both cases. Treatment involved median sternotomy in one patient and video-assisted thoracoscopy in the other. A favorable outcome was observed in both patients. The reports confirm the potential dangers related to management of sternoclavicular joint dislocation with metallic fixation devices.

Adult↗

Thoracoscopic excision of mediastinal bronchogenic cysts: results in 20 cases.

BACKGROUND: We present our experience with thoracoscopic resection of mediastinal bronchogenic cysts in adults. METHODS: From November 1990 to September 1993, 20 patients with mediastinal bronchogenic cysts were operated on by thoracoscopy. The average cyst size was 4.9 cm, and the largest diameter was 10 cm. Ten cysts were located in the middle mediastinum and 10 in the posterior mediastinum. Two cysts were complicated. RESULTS: Thirteen bronchogenic cysts were resected completely by thoracoscopy. We had to convert thoracoscopy into thoracotomy because of bleeding in two cases and because of major adhesions to vital structures in five cases. There were no operative deaths and no postoperative complications. Mean hospital stay was significantly less in the completely thoracoscopically treated group. Long-term follow-up (range, 4.5 to 7.5 years) showed no late complications and no recurrence. CONCLUSIONS: Preoperative complications, intraoperative injuries, and major adhesions to vital structures seem to be the only unfavorable conditions to thoracoscopic treatment of bronchogenic cysts. This study found encouraging results for thoracoscopic excision of mediastinal bronchogenic cysts in selected patients.

Adult↗

Comparison of the prognostic value of left ventricular filling and peak oxygen uptake in patients with systolic heart failure.

AIM: The aim of this prospective study was to compare the prognostic value of the mitral inflow pattern and peak oxygen uptake in patients with systolic heart failure. BACKGROUND: Peak oxygen uptake is a major prognostic parameter in heart failure. It is not known whether a restrictive mitral inflow pattern has similar prognostic value. METHODS: One hundred heart failure patients (ejection fraction <45%) underwent exercise testing after Doppler evaluation; prognosis was assessed after a mean follow-up of 17 months. RESULTS: The ejection fraction was larger in group 1 (non-restrictive pattern: E/A mitral wave ratio <1 or between 1 and 2 with E wave deceleration time >/=140 ms, n=45) than in group 2 (restrictive pattern: E/A ratio >2 or between 1 and 2 with E deceleration time <140 ms, n=40) (29+/-9 vs 22+/-10%, P<0.05). Peak oxygen uptake was lower in group 2 (17+/-4 vs 22+/-5 ml. min(-1). kg(-1)57+/-11 vs 75+/-15% of predicted values;P<0.05 for both comparisons). Univariate analysis showed that the deceleration time (r=0.65), E/A ratio (r=-0.50) and heart rate increment (r=0.47) correlated best with peak oxygen uptake. A third group of patients with persistent fusion of the E and A waves (n=15) had exercise responses similar to those of group 2 patients. A short deceleration time (P=0.006), a restrictive or a fusion pattern (P=0.04) were associated with a poor outcome; the prognostic value of these Doppler variables was greater than that of ejection fraction, but remained less than peak oxygen uptake indexed by predicted values (P=0.0004). CONCLUSION: The left ventricular filling pattern is a strong predictor of exercise capacity, and outcome, in patients with systolic heart failure and is independent of the left ventricular ejection fraction. Peak oxygen uptake remains a more powerful prognostic variable.

Aged↗

Impact of pulse pressure on degree of cardiac hypertrophy in patients with chronic uraemia.

OBJECTIVE: To evaluate the degree of cardiac hypertrophy in patients with end-stage renal disease (ESRD) in comparison with that in patients with uncomplicated hypertension and in patients with peripheral vascular disease (PVD), at the same values of mean blood pressure. DESIGN: Thirty-six ambulatory hypertensive patients were investigated, 11 with ESRD, 14 with PVD and 11 with uncomplicated hypertension, matched for age, sex, mean arterial pressure and antihypertensive drug treatment. METHODS: Cardiac mass was determined using M-mode echocardiography together with measurement of systemic blood pressure and the ratio between ankle and arm systolic blood pressures. RESULTS: At the same mean arterial pressure, patients with ESRD developed a greater degree of cardiac hypertrophy in comparison with those with uncomplicated hypertension (P < 0.01) and patients with PVD (P < 0.05). The pulse pressure was significantly greater in patients with ESRD than in those with uncomplicated hypertension (P< 0.01) and those with PVD (P< 0.05). Multiple regression analysis showed that only pulse pressure was positively correlated to cardiac mass (r= 0.62, P< 0.001), suggesting a predominant impact of pulse pressure on left ventricular mass in patients with ESRD. CONCLUSIONS: In patients with chronic uraemia, left ventricular hypertrophy seems to be strongly and independently associated with pulse pressure.

Blood Pressure↗

Single-pair fluorescence resonance energy transfer on freely diffusing molecules: observation of Förster distance dependence and subpopulations.

Photon bursts from single diffusing donor-acceptor labeled macromolecules were used to measure intramolecular distances and identify subpopulations of freely diffusing macromolecules in a heterogeneous ensemble. By using DNA as a rigid spacer, a series of constructs with varying intramolecular donor-acceptor spacings were used to measure the mean and distribution width of fluorescence resonance energy transfer (FRET) efficiencies as a function of distance. The mean single-pair FRET efficiencies qualitatively follow the distance dependence predicted by Förster theory. Possible contributions to the widths of the FRET efficiency distributions are discussed, and potential applications in the study of biopolymer conformational dynamics are suggested. The ability to measure intramolecular (and intermolecular) distances for single molecules implies the ability to distinguish and monitor subpopulations of molecules in a mixture with different distances or conformational states. This is demonstrated by monitoring substrate and product subpopulations before and after a restriction endonuclease cleavage reaction. Distance measurements at single-molecule resolution also should facilitate the study of complex reactions such as biopolymer folding. To this end, the denaturation of a DNA hairpin was examined by using single-pair FRET.

DNA↗

Dioxygen-activating bio-inorganic model complexes.

The study of model compounds continues to significantly contribute to our understanding of the role of transition metals at the active sites of enzymes. Recent advances in the field include the use of mimics for enzymes that activate dioxygen, as dioxygen is not only manipulated in nature but also has industrial significance in metal-catalyzed oxidations of organics. Copper, nonheme and heme iron coordination complexes have been used to mimic reversible dioxygen-binding by the three classes of blood-oxygen carriers - hemocyanin, hemerythrin and hemoglobin/myoglobin - while functional mimics of oxygenases and oxidases with copper and iron have also provided key insights into important dioxygen activation processes.

Copper↗

Effectiveness of a sanguinarine regimen after scaling and root planing.

BACKGROUND: A variety of chemical agents have been evaluated relative to their abilities to inhibit dental plaque and to improve gingival health. Chlorhexidine gluconate is the best known and most widely used member of these agents, but its long-term use is compromised by different side effects, especially extrinsic tooth and tongue staining. Another agent, sanguinarine, which is currently used in both a mouthrinse and toothpaste, leads in some cases only to a transient burning sensation and could be used on a long-term basis. The purpose of this 14-week controlled clinical trial was to assess the effectiveness of a toothpaste and oral rinse containing sanguinaria extract after scaling, root planing and a chlorhexidine regimen. METHODS: Sixty patients diagnosed as having adult periodontitis received initial periodontal therapy including scaling and root planing, followed by a 2-week oral care regimen which included rinsing with 0.2% chlorhexidine gluconate oral rinse. Upon completion of this 2-week initial therapy phase, patients were randomly assigned to either sanguinarine toothpaste and oral rinse or to control toothpaste and oral rinse without sanguinarine. Plaque (modified Quigley-Hein index) and gingivitis (gingival index) were measured prior to periodontal therapy, at the end of the chlorhexidine phase (2 weeks), and after 8 and 14 weeks. RESULTS: Sanguinarine-containing toothpaste and oral rinse significantly inhibited the redevelopment of gingivitis through the 12 weeks following the chlorhexidine phase compared to the control toothpaste and rinse. Patients in the test group had 26% fewer bleeding sites at 8 weeks, and 32% fewer at 14 weeks, than the control group. CONCLUSIONS: Our results support the combined use of chlorhexidine mouthrinse for a short term (2 weeks) followed by sanguinaria mouthrinse and toothpaste up to 3 months in order to optimize the effectiveness of chlorhexidine without side effects. Further studies on the long-term effect of this combination should be established.

Adult↗

[Cystic lymphangioma of the neck and mediastinum: are there acquired forms? Report of 37 cases].

BACKGROUND: In 9 out of 10 cases, lymphangiomas are observed during the first years of life, generally located in the neck. Rare lymphangiomas have been reported in adults, usually in an intrathoracic localization, raising the hypothesis of an acquired origin. PATIENTS AND METHODS: A retrospective analysis of patients undergoing surgery for lymphanioma of the neck or mediastinum was conducted. Pathology reports, clinical data and medical imaging (CT) were reviewed and operative and post-operative findings were analyzed in order to determine whether the cases could be divided into congenital and non-congenital forms. RESULTS: Data were obtained on 37 patients (23 men and 14 women, mean age 45 years, range 8-77). Four lesions (11%) were located in the neck: 3 in children and one in an elderly subject (77 yrs). Thirty-three tumors (89%) were located in the mediastinum. In 5 cases, the tumor was located in the phrenic nodes of the anterior mediastinum. These lymphangiomas occurred in young adults, had a CT density less than liquid with enhancement after contrast injection, and had a malformative vascular component proven anatomically and histologically (hemolymphangioma). These elements favored a congenital orgin. In 28 cases (76.6%) the tumor involved nodes in the posterior or middle mediastinum. They occurred in older adults and were purely liquid with no vascular component. These lymphangiomas were undoubtedly acquired. CONCLUSION: In children, adolescents and young adults, lymphagiomas are found in the neck or anterior mediastinum and have a tissular component. These tumors should be considered as congenital lymphangiomas. In older adults, lymphangiomas are found in the posterior or middle mediastinum and are purely liquid cysts suggesting an acquired origin.

Adolescent↗

Dissociative recombination of HD+ in selected vibrational quantum states

Rate coefficients for dissociative recombination of HD+ in selected vibrational states have been measured by a combination of two molecular fragment imaging methods by using the heavy-ion storage ring technique. Recombination fragment imaging yields state-to-state reaction rates. These rates are converted to rate coefficients by using vibrational level populations of the stored ion beam, derived from nuclear coordinate distributions measured on extracted ions. The results show strongly increasing rate coefficients for high vibrational excitation, where additional dissociation routes open up, in agreement with a theoretical calculation. Very low rate coefficients are found for certain, isolated vibrational states.

Journal Article↗

Diagnostic accuracy and prognostic value of combined dipyridamole-exercise thallium imaging in hemodialysis patients.

BACKGROUND: Non-invasive detection of coronary artery disease in dialysis patients, a major cause of mortality, often remains difficult. The aim of the study was to test the diagnostic and prognostic accuracies of combined dipyridamole-exercise thallium imaging in dialysis patients. METHODS: Dipyridamole-exercise thallium imaging and coronary angiography were both performed prospectively in 60 asymptomatic hemodialysis patients who were followed up, long term, by recording any major coronary event. RESULTS: Coronary angiography was abnormal in 13 patients (21%), and there was abnormal thallium uptake in 17 patients. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of thallium to detect a coronary artery disease were 92, 89, 71, 98 and 90%, respectively. After a median follow-up of 2.8 years, 12 patients experienced at least one major coronary event (4 cardiac deaths, 5 myocardial infarctions and 3 revascularizations). Eight of the 17 patients with abnormal thallium uptake (47%) suffered a coronary event, compared to only 4 of the 43 patients (9%) with a normal thallium uptake (P < 0.001). The positive prognostic predictive value of thallium imaging was 47% and its negative predictive value was 91%. The probability of survival free of coronary events was significantly higher in patients with normal thallium uptake than in those with abnormal thallium uptake (crude risk ratio 7.6; P < 0.001) even after adjustment for several risk factors for cardiovascular disease (adjusted risk ratio 9.2; P < 0.005). CONCLUSION: In dialysis patients, combined dipyridamole-exercise thallium imaging is an accurate method for detecting coronary stenosis and for predicting future coronary events.

Adult↗

[MRI study of the arterial ligament and the left pulmonary artery in the preoperative staging of left upper lobe bronchial cancers].

PURPOSE: To demonstrate that the ligamentum arteriosum is visible by precisely-oriented MRI. To demonstrate the predictive value of the ligament involvement for left upper lobe cancer surgery. MATERIAL AND METHODS: Fifteen controls, age-matched with bronchial cancer patients, were studied to establish how the ligamentum arteriosum could best be visualized on MRI. Visibility was optimal on RASE T1-weighted sequences on the frontal and sagittal oblique planes (aorto-pulmonary window). Acquisitions were performed with a body coil, 7 mm slices, 480 mm Fov, on a Magnetom Expert, 1T Siemens machine. Forty five patients with left upper lobe cancer underwent MRI investigation after CT had shown mediastinal proximity of the left pulmonary artery and the tumor. They underwent surgery with manual localization of the ligament at the beginning of the procedure. Findings and operative decisions were compared with those of MRI, establishing its predictive value. MRI defined the tumor-ligament and tumor first centimeters of the left pulmonary artery (LPA) relationships. RESULTS: MRI ligamentum visibility was about 87%. Ligament non-involvement on MRI (n = 23) was confirmed at surgery in all cases (100% concordance). Involvement suggested on MRI was confirmed in 18 cases and surgery was impossible or unsatisfactory. There were four false-positives with successful surgery (8% false positives). CONCLUSION: When CT shows left lobe cancers extending in the mediastinum towards the LPA, precisely-oriented MRI assesses surgical difficulty and resectability by demonstration involvement of the ligamentum and the first two centimeters of the LPA.

Adult↗