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Biomedical subjects

M H Nguyen

Publications and source records attributed to M H Nguyen.

At least 19 recordsLinked to original sources

Imaging of an enterovaginal fistula with flexible colposcopy, an endoscopic retrograde cholangiopancreatography cannula and radiographic screening.

The diagnosis of a rectovaginal or enterovaginal fistula is mostly made by a careful historical of a faecal vaginal discharge. When a rectovaginal fistula is low, an examination will demonstrate it with ease. However, when there is a high and small fistula into the vault or the fornix of the vagina, traditional methods of small bowel enema and barium enema may not demonstrate the fistula. Ultrasound and magnetic resonance imaging may demonstrate a fistula but not the nature of the bowel involved. Vaginography has been the most successful imaging method to date. Demonstrating an enterovaginal fistula and substantiating whether or not the rectum, the small bowel alone or both are implicated are important for operation planning; a fistulogram through the vagina by endoscopic method is a simple and useful adjunct to the available methods of imaging enterovaginal fistulas. We report a case and discuss a technique of endoscopic fistulography through a small fistulous opening high in the vagina. We believe that this technique is accurate, simple and complementary to vaginography in demonstrating an enterovaginal fistula.

Adult↗

Trends in BB/pellet gun injuries in children and teenagers in the United States, 1985-99.

OBJECTIVE: To characterize national trends in non-fatal BB/pellet gun related injury rates for persons aged 19 years or younger in relation to trends in non-fatal and fatal firearm related injury rates and discuss these trends in light of injury prevention and violence prevention efforts. SETTING: The National Electronic Injury Surveillance System (NEISS) includes approximately 100 hospitals with at least six beds that provide emergency services. These hospitals comprise a stratified probability sample of all US hospitals with emergency departments. The National Vital Statistics System (NVSS) is a complete census of all death certificates filed by states and is compiled annually. METHODS: National data on BB/pellet gun related injuries and injury rates were examined along with fatal and non-fatal firearm related injuries and injury rates. Non-fatal injury data for all BB/pellet gun related injury cases from 1985 through 1999, and firearm related injury cases from 1993 through 1999 were obtained from hospital emergency department records using the NEISS. Firearm related deaths from 1985 through 1999 were obtained from the NVSS. RESULTS: BB/pellet gun related injury rates increased from age 3 years to a peak at age 13 years and declined thereafter. In contrast, firearm related injury and death rates increased gradually until age 13 and then increased sharply until age 18 years. For persons aged 19 years and younger, BB/pellet gun related injury rates increased from the late 1980s until the early 1990s and then declined until 1999; these injury rates per 100 000 population were 24.0 in 1988, 32.8 in 1992, and 18.3 in 1999. This trend was similar to those for fatal and non-fatal firearm related injury rates per 100 000 which were 4.5 in 1985, 7.8 in 1993, and 4.3 in 1999 (fatal) and 38.6 in 1993 and 16.3 in 1999 (non-fatal). In 1999, an estimated 14 313 (95% confidence interval (CI) 12 025 to 16 601) cases with non-fatal BB/pellet gun injuries and an estimated 12 748 (95% CI 7881-17 615) cases with non-fatal firearm related injuries among persons aged 19 years and younger were treated in US hospital emergency departments. CONCLUSIONS: BB/pellet gun related and firearm related injury rates show similar declines since the early 1990s. These declines coincide with a growing number of prevention efforts aimed at reducing injuries to children from unsupervised access to guns and from youth violence. Evaluations at the state and local level are needed to determine true associations.

Accident Prevention↗

Himalayan tectonics explained by extrusion of a low-viscosity crustal channel coupled to focused surface denudation.

Recent interpretations of Himalayan-Tibetan tectonics have proposed that channel flow in the middle to lower crust can explain outward growth of the Tibetan plateau, and that ductile extrusion of high-grade metamorphic rocks between coeval normal- and thrust-sense shear zones can explain exhumation of the Greater Himalayan sequence. Here we use coupled thermal-mechanical numerical models to show that these two processes-channel flow and ductile extrusion-may be dynamically linked through the effects of surface denudation focused at the edge of a plateau that is underlain by low-viscosity material. Our models provide an internally self-consistent explanation for many observed features of the Himalayan-Tibetan system.

Journal Article↗

TEL-JAK2 mediates constitutive activation of the phosphatidylinositol 3'-kinase/protein kinase B signaling pathway.

A subset of chromosomal translocations that participate in leukemia involve activated tyrosine kinases. The ets transcription factor, TEL, undergoes translocations with several distinct tyrosine kinases including JAK2. TEL-JAK2 transforms cell lines to factor independence, and constitutive tyrosine kinase activity results in the phosphorylation of several substrates including STAT1, STAT3, and STAT5. In this study we have shown that TEL-JAK2 can constitutively activate the phosphatidylinositol 3'-kinase (PI 3'-kinase) signaling pathway. The regulatory subunit of PI 3'-kinase, p85, associates with TEL-JAK2 in immunoprecipitations, and this was shown to be mediated by the amino-terminal SH2 domain of p85 but independent of a putative p85-binding motif within TEL-JAK2. The scaffolding protein Gab2 can also mediate the association of p85. TEL-JAK2 constitutively phosphorylates the downstream substrate protein kinase B/AKT. Importantly, the pharmacologic PI 3'-kinase inhibitor, LY294002, blocked TEL-JAK2 factor-independent growth and phosphorylation of protein kinase B. However, LY294002 did not alter STAT5 tyrosine phosphorylation, indicating that STAT5 and protein kinase B activation mediated by TEL-JAK2 are independent signaling pathways. Therefore, activation of the PI 3'-kinase signaling pathway is an important event mediated by TEL-JAK2 chromosomal translocations.

Adaptor Proteins, Signal Transducing↗

A common epitope is shared by activated signal transducer and activator of transcription-5 (STAT5) and the phosphorylated erythropoietin receptor: implications for the docking model of STAT activation.

Erythropoietin (EPO) specifically activates the Janus kinase JAK2 and the transcription factor signal transducer and activator of transcription-5 (STAT5). All members of the STAT family are tyrosine phosphorylated in response to cytokine stimulation at a conserved carboxy-terminal tyrosine, Y694, in the case of STAT5. To determine structural features important for STAT signaling, we generated an activation-specific STAT5 antibody using a phosphopeptide containing amino acids 687 to 698 of STAT5 as antigen. This antibody specifically recognizes tyrosine- phosphorylated STAT5 but not nonphosphorylated STAT5. In immunoprecipitation reactions from cell lines and primary erythroblasts, 2 distinct polyclonal activation-specific STAT5 antibodies selectively immunoprecipitate the tyrosine phosphorylated EPO receptor (EPO-R) in addition to STAT5 under native and denaturing conditions. We propose that the activation-specific STAT5 antibody recognizes the 2 substrates to which the STAT5 SH2 domain interacts, namely, the tyrosine- phosphorylated EPO-R and STAT5 itself. Several studies have implicated EPO-R Y343, Y401, Y431, and Y479 in the recruitment of STAT5. Using a series of EPO-R tyrosine mutants expressed in Ba/F3 cells, we have shown that the activation-specific STAT5 antibody immunoprecipitates an EPO-R containing only 2 tyrosines at positions 343 and 401, confirming the importance of these tyrosines in STAT5 recruitment. These data uncover a novel aspect of STAT SH2 domain recognition and demonstrate the utility of activation-specific antibodies for examining the specificity of STAT-cytokine receptor interactions.

Animals↗

A minimal cytoplasmic subdomain of the erythropoietin receptor mediates p70 S6 kinase phosphorylation.

Erythropoietin (EPO) is a lineage-restricted growth factor that is required for erythroid proliferation and differentiation. EPO stimulates the phosphorylation and activation of p70 S6 kinase (p70 S6K), which is required for cell cycle progression. Here, the minimal cytoplasmic domains of the EPO receptor (EPO-R) required for p70 S6K activation were determined.Ba/F3 cells were stably transfected with wild-type (WT) EPO-R or EPO-R carboxyl-terminal deletion mutants, designated by the number of amino acids deleted from the cytoplasmic tail (-99, -131, -221). Transfected cells were growth factor deprived and then stimulated with EPO. p70 S6K, JAK2, IRS-2, and ERK1/2 phosphorylation/activation were examined. The ability of transfected 3-phosphoinositide-dependent protein kinase 1 (PDK1) to reconstitute p70 S6K phosphorylation in EPO-R mutants also was determined. Phosphorylation and activation of p70 S6K, JAK2, IRS-2, and ERK1/2 in Ba/F3 cells transfected with EPO-R-99 or EPO-R-99Y343F were similar to WT EPO-R. In contrast, EPO-dependent p70 S6K phosphorylation/activation, as well as IRS-2 and ERK1/2 phosphorylation, were minimal or absent in cells transfected with EPO-R-131 or EPO-R-221. JAK2 phosphorylation was reduced significantly in cells transfected with EPO-R-131 and abolished with EPO-R-221. To examine the role of PDK1, a kinase known to phosphorylate p70 S6K, Ba/F3 EPO-R-131 cells were transiently transfected with PDK1. WT constitutively active PDK1 restored p70 S6K phosphorylation in Ba/F3 EPO-R-131 cells but not in Ba/F3 EPO-R-221 cells. The results demonstrate that a minimal cytoplasmic subdomain of the EPO-R extending between -99 and -131 is required for p70 S6K phosphorylation and activation. The results also demonstrate that PDK1 is a critical component in this signaling pathway, which requires the presence of domains between -131 and -221 for its activation of p70 S6K.

3-Phosphoinositide-Dependent Protein Kinases↗

Therapeutic advances in the management of hepatitis B and hepatitis C.

Until recently, interferon monotherapy has been the only available therapeutic option for patients with chronic hepatitis B and hepatitis C. Lamivudine has emerged as another effective first-line therapy for chronic hepatitis B as well as a beneficial treatment option for patients with decompensated hepatitis B cirrhosis. Viral resistance with long-term lamivudine therapy remains a major concern but new data continue to show benefits despite the development of YMDD mutations. Combination therapy with ribavirin and pegylated interferon-alpha has revolutionized the treatment of chronic hepatitis C. The rate of sustained virological response can now be expected to be as high as nearly 50% for genotype 1 and 80% for non-1 genotypes of hepatitis C.

2-Aminopurine↗

Effect of moderate weight loss on health-related quality of life: an analysis of combined data from 4 randomized trials of sibutramine vs placebo.

OBJECTIVES: To determine whether (1) patients who experience greater weight loss also experience correspondingly greater improvements in health-related quality of life (HRQOL); (2) the improvement in HRQOL is noticeable for patients achieving moderate (5%-10%) weight reduction; and (3) the relationship between weight reduction and HRQOL is similar for patients receiving sibutramine hydrochloride vs placebo. STUDY DESIGN: We combined data from 4 double-blind, randomized, controlled trials of administration of sibutramine (20 mg/d) vs placebo. PATIENTS AND METHODS: Patients (n = 555) were mildly to moderately obese and had type 2 diabetes mellitus, dyslipidemia, or hypertension that was well controlled with an angiotensin-converting enzyme inhibitor or calcium channel blocker. The HRQOL was operationalized using the Impact of Weight on Quality of Life (IWQOL) and the Medical Outcomes Study 36-Question Short-Form (SF-36) instruments. The main statistical technique was a patient-level analysis of variance predicting change in HRQOL from study, treatment, and weight change. RESULTS: Moderate weight loss was associated with a statistically significant improvement in HRQOL for approximately half of the subscales evaluated (P < .05). The greatest sensitivity to change was shown by the SF-36 general health perception and change in health since last year subscales and the IWQOL overall health, mobility, and total subscales. Greater weight loss was associated with the most improvement in HRQOL. Weight losses of 5.01% to 10.00% were associated with 2-unit changes in the SF-36 general health perception subscale and 10-unit changes in the IWQOL total subscale. Results were similar across study and treatment. CONCLUSIONS: Moderate weight loss is associated with noticeably improved HRQOL. Improvements in HRQOL are achievable by patients receiving sibutramine.

Adult↗

Antimicrobial resistance and clinical outcome of Bacteroides bacteremia: findings of a multicenter prospective observational trial.

There is debate regarding the correlation between in vitro susceptibility testing and clinical response to therapy for Bacteroides bacteremia. We conducted a prospective multicenter observational study of 128 patients with bacteroides bacteremia. Outcome was correlated with results of in vitro susceptibility testing of Bacteroides isolates recovered from blood and/or nonblood sites, determined with use of 3 end points: mortality at 30 days, clinical response (cure vs. failure), and microbiological response (eradication vs. persistence). The mortality rate among patients who received inactive therapy (45%) was higher than among patients who received active therapy (16%; P=.04). Clinical failure (82%) and microbiological persistence (42%) were higher for patients who received inactive therapy than for patients who received active therapy (22% and 12%, respectively; P=.0002 and.06, respectively). In vitro activity of agents directed at Bacteroides species reliably predicts outcome: the specificity was 97%, and positive predictive value was 82%. Antimicrobial susceptibility testing may be indicated for patients whose blood specimens yield Bacteroides species.

Adolescent↗

Clinical manifestations and molecular epidemiology of late recurrent candidemia, and implications for management.

The aim of this study was to define the epidemiology and clinical manifestations of late recurrent candidemia. For this purpose, late recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by the same Candida sp. A total of five patients with recurrent candidemia were investigated. For all patients, isolates from the initial and recurrent episodes of candidemia were available for in vitro susceptibility testing and genetic characterization by DNA-based techniques. The results revealed the following salient features: prolonged duration between the initial and recurrent episodes (range, 1-8 months); recurrence of candidemia despite anti-fungal therapy; importance of retained intravascular catheters, neutropenia, and corticosteroids as factors predisposing to recurrence; high morbidity and mortality; no emergence of antifungal drug resistance between the initial and recurrent episodes; and relapse of infection due to the original infecting strain, rather than reinfection with a new strain. These findings raise several issues about the management and follow-up of patients with candidemia, which require assessment in future studies.

Aged↗

The different effects of black and white Vietnamese Aodai folk costumes on rectal temperature and heart rate in women walking intermittently in hot and sunny environment.

The present study was undertaken to investigate whether there is any difference in the rectal temperature and heart rate between women wearing black or white Aodai folk costume and walking intermittently in natural sunlight. The experiment was performed in the field outside buildings in Hanoi, Vietnam, between May and June, 1998. The only difference was in the colour (black or white) of clothing other physical characteristics, like materials, thickness, weight and so on, were nearly identical. Air temperature was around 39 degrees C, globe temperature around 52 degrees C and sun radiation reached 1010 W.m-2. Eight young female students (aged 20 years) participated in the experiment. They sat quietly on a chair inside the building for the first 30 min. Then they walked for 20 min at their ordinary walking speed in the sun, and rested for 10 min in the shade. This schedule was repeated three times. The main results are summarised as follows: (1) Rectal temperature was significantly lower in the black than in the white Aodai; (2) Clothing microclimate temperature at frontal chest level was also significantly lower in the black Aodai; (3) Heart rate was significantly lower in the black than in the white Aodai; (4) Clothing surface and inside temperatures measured at frontal chest level were significantly higher in the black than in the white Aodai. These results strongly suggest that the black Aodai could reduce heat strain more effectively than the white one. The physiological mechanism may result from more effective ventilation between skin and clothing in the black Aodai, due to higher temperature inside and outside this garment.

Adult↗

Nasal carriage of and infection with Staphylococcus aureus in HIV-infected patients.

BACKGROUND: Staphylococcus aureus is a common cause of serious infection in patients infected with HIV. OBJECTIVES: To evaluate risk factors for and quantitative effect of S. aureus infection in HIV-infected patients, with special attention to nasal carriage. DESIGN: Prospective, multihospital cohort study. SETTING: Three tertiary care Veterans Affairs Medical Centers. PARTICIPANTS: 231 ambulatory HIV-infected patients. RESULTS: Thirty-four percent of patients were nasal carriers of S. aureus. Of these patients, 38% were persistent carriers and 62% were intermittent carriers. Twenty-one episodes of infection occurred in 13 patients: Ten were bacteremias (including 2 cases of endocarditis), 1 was pneumonia, and 10 were cutaneous or subcutaneous infections. Seventeen (85%) of these episodes occurred in patients with CD4 counts less than 100 cells/mm3. Recurrent infections occurred in 3 of 7 patients who survived an initial S. aureus infection. The mortality rate was higher among patients with S. aureus infection than among those without infection (P = 0.03). Factors significantly associated with S. aureus infection were nasal carriage, presence of a vascular catheter, low CD4 count, and neutropenia. Molecular strain typing indicated that for 6 of 7 infected patients, the strain of S. aureus isolated from the infected sites was the same as that previously cultured from the nares. CONCLUSION: Nasal carriage is an important risk factor for S. aureus infection in HIV-infected patients. Controlled studies are indicated to determine whether eradication of nasal carriage in a selected subset of patients (for example, those with a low CD4 cell count) might prevent invasive S. aureus infection in patients with HIV infection.

AIDS-Related Opportunistic Infections↗

How large should a skin trephine be for an end stoma?

BACKGROUND: Although much has been written about techniques for making a good stoma, little has been described regarding how to excise a trephine that will perfectly fit a given end stoma. METHODS: A reproducible technique for making a stomal trephine to a precise fit for each stoma is described. RESULTS: More than 20 stomas have been made with good results. CONCLUSION: The skin trephine should have a diameter approximately two-thirds of the width of the crushed bowel end.

Colostomy↗

Correlation between in vitro susceptibility determined by E test and response to therapy with amphotericin B: results from a multicenter prospective study of candidemia.

Ninety-nine Candida bloodstream isolates underwent testing for susceptibility to amphotericin B by the E test, and the results were correlated with patients' responses to amphotericin B. The MICs for isolates that were associated with therapeutic failure were significantly higher than the MICs for those associated with therapeutic success. A MIC of >/=0.38 microgram/ml identified isolates likely to be associated with therapeutic failure.

Amphotericin B↗

Influence of incubation time, inoculum size, and glucose concentrations on spectrophotometric endpoint determinations for amphotericin B, fluconazole, and itraconazole.

We addressed the influence of the incubation time (24 h versus 48 h), starting inoculum size (standard inoculum size, approximately 10(3) CFU/ml, versus large inoculum size, approximately 10(4) CFU/ml), and supplementation with 2% glucose of RPMI 1640 medium on the spectrophotometric determination of the MICs of amphotericin B, fluconazole, and itraconazole. We compared the MICs determined spectrophotometrically with those determined by the standard broth macrodilution method (National Committee for Clinical Laboratory Standards approved guideline M27-A). The agreement between the results of the spectrophotometric and standard methods for amphotericin B testing was 100%; this agreement was independent of the inoculum size and incubation time. On the other hand, the agreement for the results for fluconazole testing and itraconazole testing was dependent on the inoculum size and incubation time. With large inoculum size, excellent agreement can be achieved at 24 h. With standard inoculum size, acceptable agreement can be achieved only at 48 h. In contrast to previous observations, the addition of 2% glucose did not have any significant impact on the growth density at 24 h, nor did it improve the agreement with the standard method. Furthermore, supplemental glucose might falsely elevate the MIC at 48 h.

Amphotericin B↗

In vitro efficacy and fungicidal activity of voriconazole against Aspergillus and Fusarium species.

Twenty-nine Aspergillus isolates and 25 Fusarium isolates underwent in vitro antifungal susceptibility testing by a broth macrodilution procedure adapted from the National Committee for Clinical Laboratory Standards guidelines. The MIC50s of both voriconazole and amphotericin B were 0.5 microg/ml and 1 microg/ml against species of Aspergillus and Fusarium, respectively, while the MIC90s of both agents were 1 and 2 microg/ml. Voriconazole was more active in vitro than amphotericin B: the geometric mean MICs of voriconazole and amphotericin B against Aspergillus spp. were 0.36 microg/ml and 0.64 microg/ml, respectively. Voriconazole also demonstrated fungicidal activity against Aspergillus spp., with 86% (24/29) of isolates exhibiting minimum lethal concentrations of < or = 4 microg/ml.

Antifungal Agents↗