KIM-HANH LE QUAN SANG - Academia.edu (original) (raw)

Papers by KIM-HANH LE QUAN SANG

Journal of Bone and Mineral Research

Circulation, Nov 23, 2010

Future Rare Diseases

What is this summary about? This is a plain language summary of an article originally published i... more What is this summary about? This is a plain language summary of an article originally published in the Journal of Bone and Mineral Research. People with fibrodysplasia ossificans progressiva (FOP) become physically disabled over time as new bone forms in places where it is not usually found, such as in muscles and ligaments. Until recently, there were no treatments for FOP that had been proven through clinical trials; however, a drug called palovarotene has been tested in clinical trials and may be effective. Here, we describe the MOVE trial, which investigated how effectively palovarotene works, as well as its safety in treating patients with FOP. What were the results? Results from MOVE suggest that palovarotene may reduce extra bone formation outside the normal skeleton. Patients with FOP who took palovarotene formed less new bone than those who did not take palovarotene. The most common side effects involved the skin, and included dryness and irritation. Some children who were s...

Journal of inherited metabolic disease, Jan 10, 2015

Alkaptonuria (AKU) is caused by deficiency of the enzyme homogentisate 1,2 dioxygenase. It result... more Alkaptonuria (AKU) is caused by deficiency of the enzyme homogentisate 1,2 dioxygenase. It results in an accumulation of homogentisate which oxidizes spontaneously to benzoquinone acetate, a highly oxidant compound, which polymerises to a melanin-like structure, in a process called ochronosis. Asymptomatic during childhood, this accumulation will lead from the second decade of life to a progressive and severe spondylo-arthopathy, associated with multisystem involvement: osteoporosis/fractures, stones (renal, prostatic, gall bladder, salivary glands), ruptures of tendons/muscle/ligaments, renal failure and aortic valve disease. The pathophysiological mechanisms of AKU remain poorly understood, but recent advances lead us to reconsider the treatment strategy in AKU patients. Besides the supporting therapies (pain killers, anti-inflammatory drugs, physiotherapy, joints replacements and others), specific therapies have been considered (anti-oxidant, low protein diet, nitisinone), but cl...

JACC: Cardiovascular Imaging, 2008

We investigated the accuracy of 64-slice computed tomography (CT) angiography, as compared to inv... more We investigated the accuracy of 64-slice computed tomography (CT) angiography, as compared to invasive angiography, to evaluate reimplanted coronary arteries in children after arterial switch operation (ASO) for transposition of the great arteries (TGA). B A C K G R O U N D Assessment of the integrity of reimplanted coronary arteries is crucial for long-term outcome after ASO for TGA. Noninvasive tests have limited accuracy for detecting significant coronary lesions, and invasive coronary angiography is usually required in this setting. M E T H O D S One hundred thirty consecutive children, after ASO for TGA (age 5.6 Ϯ 1.1 years), underwent conventional invasive coronary angiography and coronary CT angiography using a 64-slice scanner. The ability of CT to detect significant coronary stenoses (Ͼ30% diameter reduction) of the coronary ostia and proximal segments, and other abnormalities of the coronary arteries was analyzed by blinded comparison to the invasive coronary angiogram. R E S U L T S The CT was fully evaluable in 126 of 130 patients (97%), allowing assessment of ostia and proximal segments of all coronary arteries. The CT correctly detected all 12 patients (9.2%) in whom invasive coronary angiography had identified significant coronary lesions, with a sensitivity, specificity, and negative predictive value of 100%. In addition, CT showed nonsignificant coronary lesions (Ͻ30% luminal narrowing) in 6 patients and allowed determination of the underlying reasons for coronary luminal narrowing, such as stretching or compression of the re-implanted coronary arteries caused by their anatomic relationship to the adjacent great vessels. C O N C L U S I O N S 64-slice CT coronary angiography performs as well as invasive angiography for detecting significant coronary lesions in the majority of children who have undergone the arterial switch procedure for TGA. CT also provides information on the underlying mechanism of coronary luminal narrowing.

Journal of Inherited Metabolic Disease, 2019

Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also ... more Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria.

Additional file 5 Table S5: Analysis of Frequency of Conduction Abnormalities in the NHS Cohort. ... more Additional file 5 Table S5: Analysis of Frequency of Conduction Abnormalities in the NHS Cohort. Comparison of frequency of conduction abnormalities in the NHS cohort 12 month follow up data to the general population observed in Hingorani et al. [9]. Age groups are modified to be consistent. (PPTX 39 kb)

Additional file 3 Table S3: ECG Abnormalities Observed in the NHS Subjects in the 12 month follow... more Additional file 3 Table S3: ECG Abnormalities Observed in the NHS Subjects in the 12 month follow up. Frequency of general ECG readings (Normal/Abnormal/Borderline) and ECG abnormalities observed from the 12 month follow up. (PPTX 39 kb)

Additional file 2 Table S2: Comparison of cardioactive drugs to ECG results. Number of patients w... more Additional file 2 Table S2: Comparison of cardioactive drugs to ECG results. Number of patients with FOP taking potentially cardioactive drugs and the corresponding ECG result. (PPTX 42 kb)

Thrombosis and Haemostasis, 1993

SummaryEssential hypertension is often associated with high levels of plasma cholesterol or trigl... more SummaryEssential hypertension is often associated with high levels of plasma cholesterol or triglycerides. The relationships between plasma lipids and platelet lipids, membrane fluidity and functions in untreated hypertensive patients were investigated by measuring the fluorescence anisotropies of two fluorescent dyes (DPH and its cationic derivative, TMA-DPH, with different subcellular localization), cytosolic Ca2+ and pH, cyclic AMP content and aggregation to ADP and collagen. Hypercholesterolemia was found to be accompanied by a rise in platelet cholesterol content without changes in TMA-DPH or DPH anisotropies whereas hypertriglyceridemia was associated with a decreased cholesterol to phospholipid molar ratio, a decreased DPH anisotropy and a tendency of the cytosol to alkalinize. These results point out the differences between the effects of an acute cholesterol load and those of chronic hypercholesterolemia on platelet membrane microviscosity and aggregation. They demonstrate ...

Clinical Science, 1994

1. To investigate the possibility that arterial hypertension is associated with changes in the ph... more 1. To investigate the possibility that arterial hypertension is associated with changes in the physicochemical properties of cell membranes, we have studied the effects of dietary salt loading on platelet membrane microviscosity in hypertension-prone and -resistant Sabra rats. 2. Sixteen hypertension-prone and 14 hypertension-resistant Sabra rats were submitted to either a low-salt (0.25% NaCl) or a high-salt (4% NaCl) diet for 3–4 weeks. Platelet membrane anisotropy was determined, in the presence and absence of extracellular Na+, using two fluorescent probes, diphenylhexatriene and trimethylamino-diphenylhexatriene, inserted in different areas of the cell membranes. 3. A decrease in diphenylhexatriene anisotropy was demonstrated when platelets of hypertension-prone (but not hypertension-resistant) Sabra rats were suspended in a Na+-free medium. This alteration in membrane dynamic properties is localized within the hydrophobic core of the platelet membranes and is independent of sa...

American Journal of Hypertension, 1994

The altered membrane microviscosity demonstrated in various cells of spontaneously hypertensive r... more The altered membrane microviscosity demonstrated in various cells of spontaneously hypertensive rats (SHR) and essential hypertensive (EH) patients has been proposed to play an important role in the pathogenesis of genetic forms of hypertension. The aim of this study was to evaluate possible changes of membrane microviscosity in platelets and red cell ghosts of Lyon hypertensive (LH) and normotensive (LN) rats. Both erythrocyte and platelet membranes of LH rats had a clear tendency to reduced DPH fluorescence anisotropy reflecting the decreased core membrane microviscosity. On the other hand, there were no changes in TMA-DPH fluorescence anisotropy that characterizes the dynamic properties of the outer membrane leaflet. DPH, but not TMA-DPH, anisotropy correlated negatively with blood pressure. This was true for both red cell ghosts and platelets. Membrane microviscosity had no significant relationship to plasma cholesterol or triglycerides. In platelets, TMA-DPH anisotropy correlated positively with cytosolic free calcium concentration ([Ca2+]i). A similar trend was observed in erythrocytes. In contrast, DPH anisotropy had an inverse relationship to platelet [Ca2+]i. It can be concluded that the alterations of membrane microviscosity seen in LH rats are completely different from those reported in SHR animals and that surface and core membrane microviscosity differ in their relationship to blood pressure and [Ca2+]i.

Genetics in Medicine

We report the first prospective, international, natural history study of the ultra-rare genetic d... more We report the first prospective, international, natural history study of the ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). FOP is characterized by painful, recurrent flare-ups, and disabling, cumulative heterotopic ossification (HO) in soft tissues. Methods: Individuals aged ≤65 years with classical FOP (ACVR1 R206H variant) were assessed at baseline and over 36 months. Results: In total, 114 individuals participated; 33 completed the study (mean follow up: 26.8 months). Median age was 15.0 (range: 4-56) years; 54.4% were male. During the study, 82 (71.9%) individuals reported 229 flare-ups (upper back: 17.9%, hip: 14.8%, shoulder: 10.9%). After 84 days, 14 of 52 (26.9%) imaged flare-ups had new HO at the flare-up site (mean new HO volume: 28.8 × 10 3 mm 3). Mean baseline low-dose whole-body computed tomography (excluding head) HO volume was 314.4 × 10 3 mm 3 ; lowest at 2 to <8 years (68.8 × 10 3 mm 3) and increasing by age (25-65 years: 575.2 × 10 3 mm 3). The mean annualized volume of new HO was 23.6 × 10 3 mm 3 /year; highest at 8 to <15 and 15 to <25 years (21.9 × 10 3 and 41.5 × 10 3 mm 3 /year, respectively) and lowest at 25 to 65 years (4.6 × 10 3 mm 3 /year). Conclusion: Results from individuals receiving standard care for up to 3 years in this natural history study show the debilitating effect and progressive nature of FOP cross-sectionally and longitudinally, with greatest progression during childhood and early adulthood.

Additional file 4 Table S4: Conduction Abnormalities Stratified by Age from the 12 month follow u... more Additional file 4 Table S4: Conduction Abnormalities Stratified by Age from the 12 month follow up. Frequency of conduction abnormalities stratified by age from subjects at the 12 month follow up. Age stratifications based on those used in the NHS study. (PPTX 39 kb)

Summary of dosing, dose changes, and current clinical status (patients who survived to age ≥24 mo... more Summary of dosing, dose changes, and current clinical status (patients who survived to age ≥24 months). Table S2. LAL enzyme activity and LIPA genotypes. Table S3. Changes in serum transaminases, total bilirubin, and γ-glutamyltransferase (full analysis set). Table S4. Proportion of patients meeting criteria for undernutrition in the primary efficacy analysis (patients who survived to age 12 months). Table S5. Serum transaminases, hemoglobin, and albumin, most recent measurement (patients who survived to age ≥24 months). Table S6. Treatment-emergent adverse events (TEAEs) reported for two or more patients in the full analysis set. Table S7. Summary of infusion-associated reactions (IARs) in the full analysis set. (DOCX 94 kb)

The Lancet Diabetes & Endocrinology