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Biomedical subjects

H D Nguyen

Publications and source records attributed to H D Nguyen.

At least 19 recordsLinked to original sources
PubMed2005

Levosimendan for post-partum cardiomyopathy.

OBJECTIVE: To describe the use of levosimendan, a novel inotropic agent, for the treatment of post-partum cardiomyopathy (PPCMO). METHODS: The authors present the second recorded use of levosimendan for a woman with PPCMO. RESULTS: Levosimendan improved cardiac performance which was associated with symptomatic relief and echocardiographic improvement in ventricular function. The patient recovered from this episode of acute cardiac failure and continues to show steady improvement in cardiac function. CONCLUSIONS: Levosimendan proved a useful agent when used as initial therapy in this case of PPCMO.

Journal Article↗
PubMed2004

Using cartilage to repair bone: an alternative approach in tissue engineering.

Materials and techniques currently used for bone replacement/repair conform to the current paradigm, relying on bone or bone products to produce bone or induce bone formation. Yet, nature forms and heals most of the skeleton by ossification of a cartilaginous model. In this study, we cultured aggregates of E10.5 or E12 mouse embryonic limb cells in the bioreactor for 3 weeks, determined the stages of cartilage differentiation attained, and assessed the ossification and bone healing potential of the spheroids by implantation adjacent to, or directly in, a skull defect. Cultured spheroids had large cartilaginous areas, sometimes with cellular arrangements characteristic of growth plate zones. Aggregates implanted for 2 weeks adjacent to a defect mineralized and ossified (histology, micro-CT). Defects with implants had a central mass of differentiated and differentiating bone, with osteoclast activity, filling the defect. Controls had considerable remodeling on the bone edges demarcating the still present defect. This study shows that cartilage, grown in the bioreactor for 3 weeks, ossified when implanted adjacent to a bone defect, and when implanted directly in a defect, contributed to its healing. Our ability to grow differentiated bone-forming cartilage for implantation is an alternative approach in the field of bone repair.

Animals↗
PubMed2003

Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway.

Pitx2 is a bicoid-related homeodomain factor that is required for effective cell type-specific proliferation directly activating a specific growth-regulating gene cyclin D2. Here, we report that Pitx2, in response to the Wntbeta-catenin pathway and growth signals, also can regulate c-Myc and cyclin D1. Investigation of molecular mechanisms required for Pitx2-dependent proliferation, in these cases, further supports a nuclear role for beta-catenin in preventing the histone deacetylase 1-dependent inhibitory functions of several DNA-binding transcriptional repressors, potentially including E2F4p130 pocket protein inhibitory complex, as well as lymphoid enhancer factor 1 and Pitx2, by dismissal of histone deacetylase 1 and loss of its enzymatic activity. Thus, beta-catenin plays a signal-integrating role in Wnt- and growth factor-dependent proliferation events in mammalian development by both derepressing several classes of repressors and by activating Pitx2, regulating the activity of several growth control genes.

Animals↗
PubMed2002

Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.

Understanding the cell type-specific molecular mechanisms by which distinct signaling pathways combinatorially control proliferation during organogenesis is a central issue in development and disease. Here, we report that the bicoid-related transcription factor Pitx2 is rapidly induced by the Wnt/Dvl/beta-catenin pathway and is required for effective cell-type-specific proliferation by directly activating specific growth-regulating genes. Regulated exchange of HDAC1/beta-catenin converts Pitx2 from repressor to activator, analogous to control of TCF/LEF1. Pitx2 then serves as a competence factor required for the temporally ordered and growth factor-dependent recruitment of a series of specific coactivator complexes that prove necessary for Cyclin D2 gene induction. The molecular strategy underlying interactions between the Wnt and growth factor-dependent signaling pathways in cardiac outflow tract and pituitary proliferation is likely to be prototypic of cell-specific proliferation strategies in other tissues.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Percutaneous nephrolithotomy in the management of complex upper urinary tract calculi: the Singapore General Hospital experience.

INTRODUCTION AND OBJECTIVES: Presently, percutaneous nephrolithotomy (PCNL) is a well-established and effective method of treating upper urinary tract stones at our institution. The aim of this paper was to evaluate a single surgeon's four-year experience of PCNL in the Singapore General Hospital. MATERIALS AND METHODS: Between January 1996 and December 2000, 300 PCNLs were performed on 280 renal units. The mean age was 53.7 years. PCNL was performed on 57 complete staghorn calculi (20.4%), 83 partial staghorn calculi (29.6%), 66 large pelvic calculi (23.6%), 60 impacted uretero-pelvic junction (UPJ) and upper ureteric stones (21.4%) that failed extracorporeal shock wave lithotripsy (ESWL) and 14 symptomatic lower pole calculi (5%). RESULTS: The stone-free rate on discharge was 88.2% (n = 247). At 3 months and 1-year post PCNL, the stone-free rate was 91.1% (n = 255) and 95.7% (n = 268), respectively. The average postoperative stay was 4.5 days. Complications included 1 urosepsis post-PCNL (0.4%) and 2 arterio-venous fistulae (0.7%). Only 1 patient (0.4%) required blood transfusion. Thirty-four patients (12.1%) required ESWL and 4 needed ureteroscopy (1.3%). CONCLUSION: In experienced hands, the use of PCNL for upper urinary tract calculi is safe and effective.

Adult↗
PubMed2001

[Decompensation of lower limb arteritis after bone and joint surgery].

PURPOSE OF THE STUDY: Decompensation of lower limb arteritis after bone and joint surgery is an unusual finding compared with the large number of procedures performed in both emergency and controlled settings. There is however a functional and limb-threatening risk that must not be overlooked. MATERIAL AND METHODS: We report a series of 9 patients followed in our department over the last 3 years. Emergency surgery had been required in 6 patients after trauma and 3 had undergone a planned orthopedic procedure. All the patients had at least one vascular risk factor, and 7 of them had a cardiovascular history. The inaugural sign was a trophic disorder due to a grade IV decompensated arteritis in 8 patients, including 2 with nonunion. Delay to treatment ranged from 1 to 3 months. Acute embolic ischemia required emergency care in 1 patient. RESULTS: A revascularization procedure was performed on 6 limbs and was successful in 3. There were also 6 amputations, three initially, 1 after septic shock and 2 because revascularization was impossible. Three of the amputations were required after failed revascularization. Prosthesis wearing and walking was possible in only two amputated patients. Overall rate of successful salvage was 33% (3 successful revascularizations among 9 limbs). One of the nonunions healed after revascularization; the limb was amputated for the other one. One patient died from septicemia. DISCUSSION: Our series further illustrates the severity of decompensated arteritis after bone and joint surgery, emphasizing the importance of searching for cardiovascular risk factors and functional signs suggestive of a vascular disorder. Arterial duplex Doppler and if necessary arteriography of the lower limbs should be obtained in case of doubt. Two different situations can be distinguished depending on the predictable vascular risk and the localization of the planned bone reconstruction. If the patient has an asymptomatic proximal arteritis and bone and joint surgery is planned above the knee, a revascularization procedure would not appear necessary prior to bone surgery. In other cases, it may be more advisable to treat the arteritis before attempting bone surgery. For trauma victims, the osteosynthesis technique depends greatly on knowledge of the vascular risk.

Aged↗
PubMed1998

DNA methylation differences associated with tumor tissues identified by genome scanning analysis.

Most investigations on the role of DNA methylation in cancer have focused on epigenetic changes associated with known tumor suppressor genes. This may have led to an underestimation of the number of CpG islands altered by DNA methylation, since it is possible that a subset of unknown genes relevant to cancer development may preferentially be affected by epigenetic rather than genetic means and would not be identified as familial deletions, mutations, or loss of heterozygosity. We used a recently developed screening procedure (methylation-sensitive arbitrarily primed-polymerase chain reaction to scan genomic DNA for CpG islands methylated in white blood cells (WBCs) and in tumor tissues. DNA methylation pattern analysis showed little interindividual differences in the WBCs and normal epithelium (adjacent to colon, bladder, and prostate cancer cells), but with some tissue-specific differences. Cancer cells showed marked methylation changes that varied considerably between different tumors, suggesting variable penetrance of the methylation phenotype in patients. Direct sequencing of 8 of 45 bands altered in these cancers showed that several of them were CpG islands, and 2 of these sequences were identified in GenBank. Surprisingly, three of the bands studied corresponded to transcribed regions of genes. Thus, hypermethylation of CpG islands in cancer cells is not confined to the promoters of growth regulatory genes but is also found in actively transcribed regions.

Base Sequence↗
PubMed1998

The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines.

Methylation of CpG sites in the control regions of tumor suppressor genes may be an important mechanism for their heritable, yet reversible, transcriptional inactivation. These changes in methylation may impair the proper expression and/or function of cell cycle regulatory genes and confer a selective growth advantage to affected cells. Detailed methylation analysis using genomic bisulfite sequencing was performed on a series of subclones of a bladder cancer cell line in which a hypermethylated p16 gene had been reactivated by transient treatment with 5-aza-2'-deoxycytidine. Methylation of the CpG island in the promoter of the p16 gene in human bladder cancer cells did not stop the formation of a transcript initiated 20 kb upstream by the p19 promoter but did prevent the expression of a p16 transcript. Furthermore, we show that reactivant clones that expressed p16 at varying levels contained heterogeneous methylation patterns, suggesting that p16 expression can occur even in the presence of a relatively heavily methylated coding region. We also present the first functional evidence that methylation of only a small number of CpG sites can significantly down-regulate p16 promoter activity, thus providing support for the model of progressive inactivation of this tumor suppressor gene by DNA methylation.

Azacitidine↗
PubMed1998

Crystal structure of 180 degree K of bis-3, 5-diisopropylsalicylatobisdimethylsulfoxidozinc(II) and the inhibition of seizures and polymorphonuclear leukocyte chemiluminescence.

Dimethylsulfoxide (DMSO) formed a ternary complex when mixed with a Zn-3, 5-diisopropylsalicylate complex of unknown structure. The structure of this new ternary complex was characterized in an initial effort to understand the nature of this compound. Since the original complex is known to have anticonvulsant activity, the new ternary complex was also examined for anticonvulsant activity. The original complex was examined for inhibition of the polymorphonuclear leukocyte (PMNL) respiratory burst in an effort to mechanistically account for zinc complex mediated anticonvulsant activity. Dissolving the structurally unknown complex in DMSO gave crystals of a characterizable complex with an empirical formula C30H46O8S2Zn. Crystallographic data: P 1, Z = 2, a = 8.06(1), b = 12.452(2), c = 17.951(2) A, alpha = 74.42(l), beta = 77.07(1), gamma = 89.50(1) degree. The structure was refined to R = 0.03, RW = 0.04 for 3815 independent reflections with I > 2 sigma(I). This complex is mononuclear, with two 3,5-diisopropylsalicylate ligands and two bonded DMSO ligands, Zn(II)(3,5-DIPS)2(DMSO)2, Zn(II) is coordinate covalently bonded to four O atoms in a strongly distorted tetrahedral arrangement. Each DMSO ligates via its sulfoxide O atom while each 3,5-diisopropylsalicylate ligand is monodentate The non-ligating carbonyl O atom of each 3,5-DIPS is free except for an intramolecular hydrogen bond from the hydroxy group of the same ligand. Both 3,5-DIPS acid and Zn(II)(3,5-DIPS)2(DMSO)2 were examined for anticonvulsant activity in the Maximal Electroshock (MES) and Metrazol (MET) models of seizures and found to prevent both types of seizures. The Zn complex was qualitatively and quantitatively more effective than treatment with the free ligand. The influence of a Zn 3,5-DIPS complex and of the ligand 3,5-DIPS on PMNL oxidative metabolism was also studied to help understand the mechanism of anticonvulsant activity of these compounds. A dose-related and significant decrease in chemiluminescent (CL) response to opsonized Zymosan was observed, and the Zn complex was significantly more effective than the free ligand. It is concluded that mononuclear Zn complexes have anticonvulsant activity in Grand Mal and Petit Mal models of seizure possibly due to inhibition of the synthesis of superoxide or down-regulation of Nitric Oxide Synthase in activated phagocytic cells of the central nervous system.

Animals↗
PubMed1997

Synthesis and antitumor activity of the metformin platinum (IV) complex. Crystal structure of the tetrachloro(metformin)platinum (IV) dimethylsulfoxide solvate.

The synthesis of (metformin) tetrachloroplatinum (IV) was investigated (metformin is N,N-dimethylbiguanide). It crystallizes with one dimethylsulfoxide molecule as solvate in the monoclinic system, space group P2(1)/n (No. 14) with Z = 4. The cell dimensions are: a = 13.136(7), b = 9.424(2), c = 14.009(8) A, beta = 111.96(4) degrees, V = 1608.4(2) A3. Of the 4269 independent nonzero reflections collected, 1979 with I > 3 sigma (I) were considered and used in the calculations. The structure was refined to R = 0.043 and wR = 0.045. The platinum coordination is octahedral, built up from four chloride anions and one bidentate chelating ligand via the two imine nitrogen atoms cis position. The distances and angles are typical of six-membered rings that have similar donor atoms. The complex was evaluated in vitro and in vivo on murine P388 leukemia. It was found to be as potent as cis-dichlorodiammine platinum (II), CDDP, in inhibiting the proliferation of the sensitive P388 cells. However the resistant P388/CDDP cells were threefold more sensitive to the compound than to CDDP. The two compounds induced a similar perturbation in the G2+M phases of the cell-cycle. The complex was less active than CDDP in vivo on P388 leukemia when administered i.p. (intra peritoneal) on day 1.

Animals↗
PubMed1997

Defects at center P underlie diabetes-associated mitochondrial dysfunction.

Detailed respiration studies on isolated liver mitochondria from streptozotocin-induced diabetic Sprague-Dawley rats revealed a disease-associated decrease in the ADP/O ratio, a marker for mitochondrial ability to couple the consumption of oxygen to the phosphorylation of ADP. This decrease was observed following induction of respiration with glutamate/malate, succinate, or duroquinol, which enter the electron transport chain selectively at complexes I (NADH dehydrogenase), II (succinate dehydrogenase), or III (cytochrome bc1 complex), respectively. These data, coupled with studies using respiratory inhibitors (most importantly antimycin A and myxothiazol), localize at least a portion of this defect to a single site within the electron transport chain (center P in the Q-cycle portion of complex III). These results suggest that liver mitochondria from diabetic animals may generate increased levels of reactive oxygen species at the portion of the electron transport chain already established as the major site of mitochondrial free radical generation. The reduction in the ADP/O ratio occurred in mitochondria that do not have overt defects in the respiratory control ratio or in State 3 and State 4 respiration. The data in this paper suggest that defects in center P of the electron transport chain likely increase mitochondrial exposure to oxidants in the diabetic. This data may partially explain the evidence of altered exposure and/or response to reactive species in mitochondria from diabetics. This work thus provides further clues to the interaction between oxidative stress and diabetes-associated mitochondrial dysfunction.

Adenosine Diphosphate↗
PubMed1995

The effect of contrast dose, imaging time, and lesion size in the MR detection of intracerebral metastasis.

PURPOSE: To evaluate the effect of MR contrast dose versus delayed imaging time on the detection of metastatic brain lesions based on lesion size. METHODS: Contrast MR examinations with gadoteridol were obtained in 45 patients with brain metastases. The patients were divided into two groups: 16 received cumulative standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg). Both groups were evaluated at two dose levels (lower dose and higher dose) with two separate injections. Each patient received an initial bolus injection of either 0.05 (cumulative standard dose) or 0.1 (cumulative triple dose) mmol/kg of gadoteridol to reach the lower-dose level and underwent imaging immediately and 10 and 20 minutes later. Thirty minutes after injection, an additional bolus injection of 0.05 (cumulative standard dose) or 0.2 (cumulative triple dose) mmol/kg was administered to reach the cumulative higher-dose level (cumulative standard dose, 0.1 mmol/kg; cumulative triple dose, 0.3 mmol). Images were acquired immediately. RESULTS: There was no difference in the detection rate for lesions larger than 10 mm among T2-weighted, lower-dose immediate and delayed, or immediate higher-dose images in both study groups. Lesions smaller than 10 mm had improved detection with delayed imaging in both study groups; however, the immediate higher-dose studies still had the highest detection rate. CONCLUSION: In the evaluation of small central nervous system metastases, either delayed imaging after the injection of standard contrast dose or higher contrast dose may improve their detection, and therefore affect clinical management. Higher contrast dose (cumulative triple dose) studies appear to be more effective than delayed imaging with standard dose.

Brain↗
PubMed1994

Brain parenchymal infection in bone marrow transplantation patients: CT and MR findings.

OBJECTIVE: The purpose of this study was to assess the MR and CT appearance of brain infection after bone marrow transplantation and to correlate the appearances with laboratory and pathologic findings. MATERIALS AND METHODS: We retrospectively reviewed the records of seven bone marrow transplant recipients with radiologic evidence of brain infection. RESULTS: Forty-one lesions were detected in seven patients with proved infectious foci outside the brain before brain infection was suspected clinically. Six patients had low total WBC or lymphocyte counts and one patient had normal total WBC and lymphocyte counts. Most lesions in patients with low total WBC or lymphocyte counts showed no appreciable edema or contrast enhancement. However, all lesions detected in the patient with normal total WBC and lymphocyte counts showed marked vasogenic edema and ring enhancement. CONCLUSION: Brain infection in bone marrow transplant recipients during immunosuppression exhibited MR characteristics different from those typically seen in immunocompetent patients. This appearance may be related to a diminished immunologic/inflammatory response.

Adult↗
PubMed1994

Delineation of gliomas with various doses of MR contrast material.

PURPOSE: To examine the effects of different gadolinium doses on the delineation of gliomas, particularly the demonstration of abnormal enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality on corresponding T2-weighted images. METHODS: During phase II clinical trials of gadoteridol, 23 patients with pathologically proved gliomas were studied by MR with various doses of gadoteridol, ranging from 0.05 to 0.3 mmol/kg. RESULTS: All of the gliomas were readily detected by T2-weighted images. Twelve of 23 patients demonstrated enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality demonstrated on T2-weighted images. These findings were seen in none of the six patients (0%) studied at 0.05 mmol/kg, one of five patients (20%) studied at 0.1 mmol/kg, four of five patients (80%) studied at 0.2 mmol/kg, and seven of seven patients (100%) studied at 0.3 mmol/kg. CONCLUSIONS: The detection of symptomatic gliomas does not require a contrast agent because they are generally large and readily demonstrated on T2-weighted images. However, the area of postcontrast enhancement of gliomas seems to be greater with higher doses of contrast agent. The cause of the abnormal enhancement extending beyond the zone of apparent signal abnormality on T2-weighted images seen in this limited study is unknown and probably represents tumor infiltration. The frequency of detection of such findings appears to be proportional to the dose of contrast material used.

Brain↗
PubMed1994

Cost-effectiveness of high-dose MR contrast studies in the evaluation of brain metastases.

PURPOSE: To investigate the cost-effectiveness of high-dose MR contrast studies in the management of brain metastases. METHODS: During the phase III clinical trial of high-dose contrast studies (0.3 mmol/kg), 11 of 27 patients were judged by the reviewers to have potential treatment changes based on the additional information provided by the high-dose studies. We retrospectively evaluated how many of these 27 patients had actual treatment changes because of the results of the high-dose study. Using the fee schedule at our institution, the cost-effectiveness was analyzed based on the cost savings from treatment changes and the additional expense of implementing the high-dose studies. RESULTS: A total of 3 craniotomies ($22,800 each) and 2 aggressive courses of radiation therapy ($1122 each) were avoided in 4 patients because of the additional lesions detected by the high-dose studies. This resulted in a treatment cost savings of $70,644. The extra expense for implementing the high-dose study is $9126 for a single injection in all 27 patients, $9295 for 2 separate injections completed in 1 visit in the 11 patients, and $11,154 for 2 separate injections completed in 2 separate visits. The cost savings in management (diagnosis and treatment) therefore ranged from $59,490 to $61,518 for all patients and from $2203 to $2278 per patient. CONCLUSION: Based on our limited data, the high-dose study seems to impact positively on the cost-effectiveness in the management of brain metastases. However, because our study had limitations, our results need to be confirmed with a larger patient population and a more standardized treatment approach and fee schedule.

Adult↗
PubMed1994

Sequential MR enhancement pattern in normal pituitary gland and in pituitary adenoma.

PURPOSE: To measure and evaluate the temporal enhancement characteristics of the normal pituitary gland and pituitary adenoma. METHODS: Thirty healthy subjects and 10 patients with sellar pituitary adenomas were studied prospectively using dynamic MR imaging with a 5- or 10-sec temporal resolution during a bolus injection of gadolinium. RESULTS: Qualitative visual analysis demonstrated a consistent sequential pattern of pituitary enhancement in which the posterior lobe enhanced earlier than the anterior lobe by approximately 35 sec. Quantitative analysis revealed that posterior lobe enhancement occurred 9.8 +/- 1.5 sec (mean +/- SEM) before the anterior lobe in healthy subjects, whereas tumor enhancement occurred significantly before the anterior lobe but only slightly before the posterior lobe in patients with adenomas. CONCLUSION: The sequential enhancement pattern of the normal pituitary gland was found to be consistent with its vascular anatomy. In contrast to previous reports, pituitary adenomas were found to enhance earlier than the anterior lobe. These results suggest that pituitary adenomas have a direct arterial blood supply, similar to that of the posterior pituitary lobe.

Adenoma↗