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Biomedical subjects

T H Nguyen

Publications and source records attributed to T H Nguyen.

At least 19 recordsLinked to original sources

[Septic shock due to vancomycin-resistant enterococci infection. Tigecycline monotherapy].

Adequate antimicrobial therapy is of crucial importance for the survival of critically ill patients with severe nosocomial infections. Tigecycline is an important therapeutic option for the treatment of infections caused by multi-resistant Gram-positive and Gram-negative bacteria including vancomycin-resistant enterococci (VRE). A large randomised study (patients with APACHE-II-score >30 excluded/mean APACHE-II-score 6) demonstrated that tigecycline is not inferior to imipenem/cilastatin for treatment of complicated intra-abdominal infections. However, no case has been reported with microbiological eradication and clinical cure in a patient with septic shock due to peritonitis caused by VRE and treatment with tigecycline monotherapy. Clinical details of a patient suffering from postoperative peritonitis are presented. The patient developed severe septic shock after pancreatic surgery (multiple organ failure, APACHE-II-score 34). As the site of anastomotic leakage was very small and could not be exactly identified, irrigation-suction drains were placed followed by closed postoperative continuous lavage. The pathogen responsible was identified as a vancomycin-resistant Enterococcus faecium, therefore monotherapy with tigecycline was started which resulted in microbiological response and clinical cure. Tigecycline is a new therapeutic option for the treatment of intra-abdominal infections and from an economic point of view financially rewarding when used as monotherapy.

APACHE↗

Hypoglycemia leads to age-related loss of vision.

The retina is among the most metabolically active tissues in the body, requiring a constant supply of blood glucose to sustain function. We assessed the impact of low blood glucose on the vision of C57BL/6J mice rendered hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr. Metabolic stress from moderate hypoglycemia led to late-onset loss of retinal function in Gcgr(-/-) mice, loss of visual acuity, and eventual death of retinal cells. Retinal function measured by the electroretinogram b-wave threshold declined >100-fold from age 9 to 13 months, whereas decreases in photoreceptor function measured by the ERG a-wave were delayed by 3 months. At 10 months of age Gcgr(-/-) mice began to lose visual acuity and exhibit changes in retinal anatomy, including an increase in cell death that was initially more pronounced in the inner retina. Decreases in retinal function and visual acuity correlated directly with the degree of hypoglycemia. This work demonstrates a metabolic-stress-induced loss of vision in mammals, which has not been described previously. Linkage between low blood glucose and loss of vision in mice may highlight the importance for glycemic control in diabetics and retinal diseases related to metabolic stress as macular degeneration.

Age Factors↗

Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet.

BACKGROUND: A dietary portfolio of cholesterol-lowering ingredients has proved effective in reducing serum cholesterol. However, it is not known whether this dietary combination will also affect hematologic risk factors for coronary heart disease (CHD). Reductions in hematocrit and polymorphonuclear leukocytes have been reported to improve cardiovascular risk. We, therefore, report changes in hematological indices, which have been linked to cardiovascular health, in a 1-year assessment of subjects taking an effective dietary combination (portfolio) of cholesterol-lowering foods. METHODS: For 12 months, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (23 g/1000 kcal). Fifty-five subjects completed the study. RESULTS: Over the 1 year, data on completers indicated small but significant reductions in hemoglobin (-1.5+/-0.6 g/l, P=0.013), hematocrit (-0.007+/-0.002 l/l, P<0.001), red cell number (-0.07+/-0.02 10(9)/l, P<0.001) and neutrophils (-0.34+/-0.13 10(9)/l, P=0.014). Mean platelet volume was also increased (0.16+/-0.07 fl, P=0.033). The increase in red cell osmotic fragility (0.05+/-0.03 g/l, P=0.107) did not reach significance. CONCLUSIONS: These small changes in hematological indices after a cholesterol-lowering diet are in the direction, which would be predicted to reduce CHD risk. Further research is needed to clarify whether the changes observed will contribute directly or indirectly to cardiovascular benefits beyond those expected from reductions previously seen in serum lipids and blood pressure.

Adult↗

Multi-detector row CT scanning in Paleoanthropology at various tube current settings and scanning mode.

The purpose of this study was to determine the optimal tube current setting and scanning mode for hominid fossil skull scanning, using multi-detector row computed tomography (CT). Four fossil skulls (La Ferrassie 1, Abri Pataud 1, CroMagnon 2 and Cro-Magnon 3) were examined by using the CT scanner LightSpeed 16 (General Electric Medical Systems) with varying dose per section (160, 250, and 300 mAs) and scanning mode (helical and conventional). Image quality of two-dimensional (2D) multiplanar reconstructions, three-dimensional (3D) reconstructions and native images was assessed by four reviewers using a four-point grading scale. An ANOVA (analysis of variance) model was used to compare the mean score for each sequence and the overall mean score according to the levels of the scanning parameters. Compared with helical CT (mean score=12.03), the conventional technique showed sustained poor image quality (mean score=4.17). With the helical mode, we observed a better image quality at 300 mAs than at 160 in the 3D sequences (P=0.03). Whereas in native images, a reduction in the effective tube current induced no degradation in image quality (P=0.05). Our study suggests a standardized protocol for fossil scanning with a 16 x 0.625 detector configuration, a 10 mm beam collimation, a 0.562:1 acquisition mode, a 0.625/0.4 mm slice thickness/reconstruction interval, a pitch of 5.62, 120 kV and 300 mAs especially when a 3D study is required.

Adult↗

MR tractography with diffusion tensor imaging in clinical routine.

Using MRI, we demonstrated that the depiction of the cerebral white matter fiber tracts has become a routine procedure. Diffusion tensor (DT) sequences may be analyzed with combined volume analysis and tractography extraction software, giving indirect visualization of white matter connections. We obtained DT data from 20 subjects with normal MR imaging and five patients presenting cerebral diseases such as brain tumors, multiple sclerosis and stroke, with five patients explored on two different MR scanners. Data were transferred to dedicated workstations for anatomical realignment, determination of voxel eigenvectors and calculation of fiber tract orientations in a region of interest. In all subjects, axonal directions underlying the main neuronal pathways could be delineated. Comparisons between diseased regions and contralateral areas demonstrated changes in voxel anisotropy in injured regions, revealing possible preferential fiber orientations within diffuse T2 hyperintensities. Rapid data processing allows imaging of the normal and diseased fiber pathways as part of the routine MRI examination. Therefore, it appears that whenever white matter disease is suspected a tractography can be performed with this fast and simple method that we proved to be reliable and reproducible.

Adult↗

2-Chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) exhibits p53-dependent and -independent antiproliferative activity in human nasopharyngeal carcinoma cells in vitro and in vivo.

2-Chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) has been used to treat patients with advanced solid tumours. However, the molecular mechanisms are not well understood. In the present study, we report that SarCNU inhibited proliferation of human HK-1 and CNE-2 nasopharyngeal carcinoma (NPC) in vivo and in vitro. In vitro study showed that wild-type p53 HK-1 cells were 3-fold more sensitive to SarCNU than p53 mutant CNE-2 cells. G2/M arrest, reduction in p21(Cip1/Waf1) and inactivation of cellular cdc-2 activity were seen in both SarCNU-treated HK-1 and CNE-2 cells. Upregulation of p53, phosphorylated p53 at Ser15 and biochemical markers for apoptosis, such as cleaved caspase-3, cleaved caspase-7 and cleaved PARP, were observed in SarCNU-treated HK-1 but not CNE-2 cells. The levels of cyclin B1, Wee1 and phosphorylated cdc-2 but not total cdc-2 in HK-1 cells were significantly reduced by SarCNU treatment. In contrast to HK-1 cells, decrease in total cdc-2 but increase in phosphorylated cdc-2 at Tyr15, cyclin B1 and Wee1 was observed in CNE-2 cells treated with SarCNU. Introduction of mutant p53 into HK-1 cells resulted in growth enhancement in vivo and increased resistance to SarCNU-induced apoptosis in vitro. Furthermore, CNE-2 cells transfected with wild-type p53 became susceptible to SarCNU-induced apoptosis in vitro but not their growth rate in vivo. The data indicate that in NPC cells SarCNU-induced apoptosis was p53-dependent while SarCNU-induced G2/M arrest was mediated by altering the levels of cyclin B1-cdc-2 complex and phosphorylation of cdc-2 at Tyr15 resulting in inactivation of cellular cdc-2 activity. Our data suggest a potential use of SarCNU in the treatment of NPC.

Animals↗

[Manufacturing and stability of copper-histidine solution for treatment of Menkes' Kinky Hair Syndrome].

Menkes' Kinky Hair Syndrom is a rare, X-linked recessive multisystemic lethal disorder of copper metabolism. Male infants who are affected usually die at the age of 2-3 years. If the disease is diagnosed early, patients profit from subcutaneously administered copper salts. We describe the preparation and stability of a copper-histidin solution. This solution has some advantages in terms of stability over the solutions described in earlier publications. This is a great advantage for the patients and their parents, because an ambulatory care or a home care of this patients is possible now.

Copper↗

Specific neocerebellar activation during out-of-phase bimanual movements.

We used fMRI to study cerebellar activation during index finger-thumb opposition of the right hand and index finger-thumb opposition of both hands in in-phase and out-of-phase modes. The right hand movement activates the contralateral anterior lobe of the cerebellum. During bimanual in-phase movements, this activity pattern becomes bilateral. More interestingly, bilateral out-of-phase movements recruit the cerebellar posterior lobe VIII, which likely corresponds to the second homunculus. As out-of-phase movements differ from the in-phase movements only by their temporal complexity and their attentional awareness, this study demonstrates the preferential involvement of the cerebellar second homunculus in the control of complex movements.

Adult↗

Liver gene therapy: advances and hurdles.

Liver gene therapy is being developed as an alternative to orthotopic liver transplantation, which is the only effective therapy for many liver diseases. The liver has unique features that make it attractive for in vivo and ex vivo gene transfer. In vivo approach is far less invasive than ex vivo approach, although in most cases, host immune response directed against the transgene product and/or vector particles severely impairs the efficiency of gene transfer, and precludes long-term transgene expression after in vivo gene delivery. Ex vivo approach allows for an elective targeting of the hepatocytes, avoiding that the transgene be expressed in professional antigen-presenting, but is faced with the low in vitro proliferative ability of hepatocytes, and to the low in vivo liver repopulating ability of transplanted cells. In some specific situations where immune response was controlled or transplanted cells had a strong growth advantage over host hepatocytes, gene transfer resulted in long-term and complete correction of a liver genetic defect. In this review, we will outline the liver diseases that may benefit from gene therapy, the vector technology under investigation, the advances and the problems to be overcome.

Animals↗

Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Southeast Asia. Hyperphosphorylation of retinoblastoma (pRB) by cyclin/CDKs in G1/S transition is required for its inactivation and cell cycle progression. In the present study, we report that phosphorylation of pRB at Ser780 and Ser795 was detected in 71% (33 of 46) and 63% (29 of 46) of HCCs examined respectively. pRB protein was undetectable in 13% (6 of 46) of HCCs examined. Phosphorylated pRB was localized in the nuclei of hepatocarcinoma cells. Benign hepatocytes exhibited very weakly or no nuclear staining for phosphorylated pRB. Over-expression of E2F-1, cyclin D1, Cdk-2, Cdk-4 and cyclin A was found in 64% (30 of 46), 43% (26 of 46), 28% (11 of 46), 71% (33 of 46) and 63% (29 of 46) of HCCs examined respectively and this was correlated with elevation of ERK. Treatment of HepG2 cells with MEK1/2 inhibitor U0126 resulted in cell cycle arrest, downregulation of cyclin D1 and Cdk-2 expression and inhibition of pRB phosphorylation at Ser780 and Ser795. Ectopic expression of activated MEK1 in HepG2 cells increased cyclin D1 and Cdk-2 expression, phosphorylation of pRB at Ser780 and Ser795, and percentage of cells in S phase. Our data indicate that activated ERK plays an important role in cyclin D1 and Cdk-2 expression and phosphorylation of pRB at Ser780 and Ser795 in liver cancer cells.

CDC2-CDC28 Kinases↗

The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells.

Dietary phytochemicals have been shown to be protective against various types of cancers. However, the precise underlying protective mechanisms are poorly understood. In the present study, we report that treatment of A549 cells with quercetin resulted in a dose-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 1.2 +/- 0.8, 6.3 +/- 0.9, 16.5 +/- 1.5, 36.4 +/- 2.6 and 42.5 +/- 5.8% on treatment with 0.1% dimethylsulfoxide, 14.5, 29.0, 43.5 and 58.0 micro M quercetin, respectively. Concomitantly, quercetin treatments led to a 1.1-, 1.1-, 2.5- and 3.5-fold increase in Bax. Similar elevations were also observed in Bad, which increased 1.1-, 2.1-, 2.2- and 2.3-fold, respectively, as compared with control. While Bcl-2 was decreased by 30%, Bcl-x(L) was elevated in a dose-dependent fashion. Quercetin also induced the cleavage of caspase-3, caspase-7 and PARP (poly ADP-ribose polymerase). While Akt-1 and phosphorylated Akt-1 were inhibited, the extracellular signal-regulated kinase (ERK) was phosphorylated following quercetin treatment in a dose-dependent fashion. Phosphorylation of ERK and c-Jun occurred at 3 h and was sustained over 14 h. Phosphorylation of MEK1/2 was increased in concordance with ERK activation. Quercetin-induced phosphorylation of c-Jun N-terminal kinase (JNK) and cleavage of caspase-3 occurred 6 h after quercetin exposure and before cleavage of caspase-7 and PARP was detected. Inhibition of MEK1/2 but not PI-3 kinase, p38 kinase or JNK abolished quercetin-induced phosphorylation of c-Jun, cleavage of caspase-3 and -7, cleavage of PARP and apoptosis. Inhibition of caspase activation completely blocked quercetin-induced apoptosis. Expression of constitutively activated MEK1 in A549 cells led to activation of caspase-3 and apoptosis. The results suggest that in addition to inactivation of Akt-1 and alteration in the expression of the Bcl-2 family of proteins, activation of MEK-ERK is required for quercetin-induced apoptosis in A549 lung carcinoma cells.

Apoptosis↗

Plastic wound protectors do not affect wound infection rates following laparoscopic-assisted colectomy.

BACKGROUND: Wound protectors are plastic sheaths that can be used to line a wound during surgery. Wound protectors can facilitate retraction of an incision without the need for other mechanical retractors and have been proposed as deterrents to wound infection. The purpose of this study was to define the ability of wound protectors to reduce the rate of infection when used in laparoscopic-assisted colectomy. METHODS: We completed a retrospective review of the medical records of patients undergoing nonemergent laparoscopic-assisted colectomy between February 1999 and November 2002. All completely laparoscopic cases were excluded. The wound protector, when used, was applied to the extraction incision during the externalized portion of the procedure (colon and mesentery transection, anastomosis). Outcomes for patients with and without the use of a wound protector were compared. RESULTS: A total of 141 patients underwent laparoscopic-assisted colectomy (98 for benign/malignant tumors, 35 for diverticular disease, and eight for Crohn's disease). There were no differences between the wound protector group ( n = 84) and the no wound protector group ( n = 57) with respect to mean age (55 vs 58 years), average body mass index (27 vs 29 kg/m2), gender, indication for surgery, comorbidities, antibiotics used, or mean operative time (185 vs 173 min). Nine patients in the wound protector group and eight in the no wound protector group developed a wound infection at the colon extraction site ( p = 0.42). Patients undergoing resection for Crohn's disease or diverticulitis had a higher infection rate (18.6%) than patients undergoing resection for polyps or cancer (9.2%; p < 0.05). No wound recurrence of cancer was observed in either group at a mean follow-up of 23 months (range, 3-48). CONCLUSIONS: The wound protector, although useful for mechanical retraction of small wounds, does not significantly diminish the rate of wound infection at the bowel resection/anastomotic site. Patients undergoing elective resection for inflammatory processes have higher infection rates than patients undergoing laparoscopic-assisted colectomy for polyps or cancer.

Adult↗

Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK.

A vast variety of naturally occurring substances have been shown to protect against experimental carcinogenesis and an increasing amount of evidence suggests that kaempferol may have cancer chemopreventative properties. However, the precise underlying protective mechanisms are poorly understood. To elucidate these mechanisms, we challenged human lung cancer cell line A549 with kaempferol and investigated its effects upon cellular growth and signal transduction pathways. Treatment of A549 cells with kaempferol resulted in a dose- and time-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 0.9+/-0.5, 5.2+/-1.5, 16.8+/-2.0, 25.4+/-2.6, and 37.8+/-4.5% on treatment with 0, 17.5, 35.0, 52.5, and 70.0 microM kaempferol, respectively. Concomitantly, kaempferol treatments led to a 1.2-, 2.7-, 3.3-, and 3.4-fold increase in Bax. Similar elevations were also observed in Bad which increased 1.2-, 3.3-, 3.7-, and 4.7-fold, respectively, as compared to control. Bcl-2 and Bcl-xL expression were inhibited in a dose-dependent fashion. While the Akt-1 and phosphorylated Akt-1 were inhibited, the mitogen-activated protein kinase (MAPK) was activated upon kaempferol treatment. Kaempferol induced apoptosis was associated with the cleavage of caspase-7 and poly ADP-ribose polymerase (PARP). Inhibition of MEK1/2 but not PI-3 kinase blocked kaempferol-induced cleavage of caspase-7, PARP cleavage, and apoptosis. The results suggest that inactivation of Akt-1 and alteration of Bcl-2 family of proteins are not sufficient for kaempferol to induce apoptosis and activation of MEK-MAPK is a requirement for kaempferol-induced cell death machinery in A549 cells.

Antineoplastic Agents↗

Recovery from gastric mucus depletion in the intact guinea pig mucosa.

BACKGROUND: In developed countries one-third of the population is infected with the gastric pathogen Helicobacter pylori. In the early stages of H. pylori-induced gastritis, typical symptoms include gastric erosions and mucus depletions. Artificial mucus depletion was generated, demonstrating both consequent irritation and recovery processes in the mucosa. METHODS: The mucus depletion was examined by removing a small cylinder of mucus from the surface of the explanted guinea pig corpus mucosa, leaving the epithelial surface intact. pH microelectrodes were inserted into the mucosa in vitro, measuring the epicellular mucus pH, the pH(i) of the underlying epithelial cells and the pH inside the gastric glands during mucus regeneration. Using infrared microscopy, the same process of mucus layer renewal was followed in anaesthetized animals. RESULTS: The depletion exposed the tissue surface to low luminal pH levels. At a luminal pH of 2.5, a decrease was observed in the crypt outlet pH and surface cell pH(i), while deeper cells were less affected. However, a subsequent neutralization in the deep gland lumen was found. During the repair process, a quarter of the mucus layer was regenerated within the first 5 min. This newly secreted mucus formed a structure similar to that before depletion. Within 45 min, pH(i) and tissue-near pH values had fully recovered. CONCLUSION: Following mucus depletion, there is a decrease in surface cell pH(i) and crypt outlet pH values. The repair process is then characterized by extensive mucus secretion and local cessation of acid secretion.

Animals↗

[Tractography of the visual pathways: routine examination in magnetic resonance imaging].

Water diffusion analysis in magnetic resonance imaging (MRI) provides an elective visualization of fiber tract orientations in cerebral white matter, especially for optic tracts. We explored 25 patients from 18 to 45 years of age, with normal MRI in 20 subjects, and radiological anomalies in five. On a 1.5 Tesla MRI apparatus, diffusion tensor acquisitions were performed in 5 minutes 58 seconds with an EPI Single Shot sequence covering the entire brain. Image displacements were precluded by patient information and adequate fixation, then digitally corrected on workstations. Volume merging and fiber tract extraction were achieved using dedicated software (Volume-One and dTV). A directional depiction was obtained for all areas in the white matter, in particular for white matter junctions. Coming from the lateral geniculate body, the optic tracts were directed posteriorly toward the occipital cortex, with numerous connections to extrastriate associative areas, and through the corpus callosum and the fornix. Diffusion tractography requires optimization of volume displacements, before and secondary to MRI acquisitions. Our diffusion tensor acquisition, with image optimization in a short-duration sequence can be routinely applied to all patients, for a specific analysis of functional connections between cortical areas of cerebral white matter.

Adolescent↗

The epidemiology and disease burden of rotavirus in Vietnam: sentinel surveillance at 6 hospitals.

The disease burden of rotavirus diarrhea in Vietnam was assessed by surveillance of children <5 years old who were hospitalized for diarrhea at 3 centers in the north and 3 centers in the south. Rotavirus was identified in 56% (range, 47%-60%) of the 5768 patients surveyed between July 1998 and June 2000. G-typing of the first 224 strains indicated that only 2% were non-typeable, 9% were in mixed infections, and the remainder were of the common serotypes G1, G2, G3, G4, and G9. In Vietnam, diarrhea accounts for 9880 deaths per year, which is approximately 15% of all deaths among children <5 years old, or 6.5 deaths per 1000 children. If even 50% of these diarrhea-related deaths in Vietnam were due to rotavirus, the number would represent 4%-8% of all deaths among children <5 years old, 2700-5400 rotavirus-related deaths per year, and 1 death per 280-560 children during the first 5 years of life. Thus, the disease burden of rotavirus in Vietnam is substantial, and programs to encourage the use of oral rehydration should be encouraged while efforts to develop vaccines continue.

Age Distribution↗

Identification of a matrix-degrading phenotype in human tuberculosis in vitro and in vivo.

Tuberculous meningitis is characterized by cerebral tissue destruction. Monocytes, pivotal in immune responses to Mycobacterium tuberculosis, secrete matrix metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across the blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic (THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a dose-dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239 +/- 75 ng/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24--48 h. In contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene expression and secretion were similar to constitutive levels from controls at 24 h and increased just 5-fold by 48 h. In vivo investigation revealed MMP-9 concentration per leukocyte in cerebrospinal fluid (CSF) from tuberculous meningitis patients (n = 23; median (range), 3.19 (0.19--31.00) ng/ml/cell) to be higher than that in bacterial (n = 12; 0.23 (0.01--18.37) ng/ml/cell) or viral meningitis (n = 20; 0.20 (0.04--31.00) ng/ml/cell; p < 0.01). TIMP-1, which was constitutively secreted into CSF, was not elevated in tuberculous compared with bacterial meningitis or controls. Thus, a phenotype in which MMP-9 activity is relatively unrestricted by TIMP-1 developed both in vitro and in vivo. This is functionally significant, since MMP-9 concentrations per CSF leukocyte (but not TIMP-1 concentrations) were elevated in fatal tuberculous meningitis and in patients with signs of cerebral tissue damage (unconsciousness, confusion, or neurological deficit; p < 0.05). However, MMP-9 activity was unrelated to the severity of systemic illness. In summary, M. tuberculosis-infected monocytic cells develop a matrix-degrading phenotype, which was observed in vivo and relates to clinical signs reflecting cerebral injury in tuberculous meningitis.

Adult↗