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Biomedical subjects

D Chien

Publications and source records attributed to D Chien.

At least 37 records · Page 2Linked to original sources
PubMed1994

Hepatitis C virus markers in patients with long-term biochemical and histological remission of chronic hepatitis.

We measured hepatitis C virus (HCV) RNA and antibodies against HCV recombinant proteins (C22/S1, E1/S2, E2/NS1, C33/NS3, C100/NS4, NS5) in serial serum samples from 22 interferon-treated patients with a long-term follow up (range: 36-44 months). Eleven of them showed persistently normal liver function tests and a significant histological amelioration or a complete resolution of chronic hepatitis (long-term responders, LTRs). In the remaining 11 patients (non-responders (NRs)) liver function tests normalized temporarily during therapy or remained unchanged. At the end of the follow up (3 years), viraemia was undetectable in six of 11 LTRs (54.6%). HCV-RNA was always detectable in the serum of NRs (p = 0.017). At admission, anti-C22/S1, anti-E1/S2, anti-E2/NS1, anti-C33/NS3, anti-C100/NS4 and anti-NS5 were detected in 95.4%, 40.9%, 77.3%, 95.4%, 72.7% and 77.3% of the patients, respectively. Three years after suspension of therapy, anti-C100/NS4 was undetectable in five of six (83.3%) LTRs who cleared HCV-RNA and in only one with ongoing viraemia (20%). Anti-E2/NS1 was undetectable in 54.5% of LTRs and in no NRs (p = 0.067). Anti-E1/S2 was detected more frequently in LTRs than in NRs (81.8% vs 45.5%). Serum levels of anti-C22/S1, C33/NS3 and NS5 did not change during therapy and the follow up in either group of patients. The clearance of viraemia in LTRs was associated with that of anti-C100/NS4 (p = 0.017). Serum HCV-RNA and anti-C100/NS4 appear suitable tools for monitoring patients who respond to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Evidence for hepatitis C viral infection in patients with primary hepatocellular carcinoma.

In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States.

Adult↗
PubMed1993

Double-blind; placebo-controlled trial of piperacillin prophylaxis in preterm membrane rupture.

OBJECTIVE: We attempted to test whether antibiotic therapy prolongs pregnancy in preterm premature rupture of membranes, because preterm premature rupture of membranes is frequently associated with chorionic-decidual infection. STUDY DESIGN: Women with preterm premature rupture of membranes and a singleton gestation at 24 to 34 completed weeks were randomized to receive either piperacillin 3 gm or placebo intravenously every 6 hours for 72 hours and were managed conservatively until spontaneous delivery, chorioamnionitis, or fetal distress. RESULTS: Between January 1987 and January 1992, a total of 75 patients were randomized to receive piperacillin (n = 38) or placebo (n = 37). There were no differences between the piperacillin group and the placebo group in mean gestational age at randomization (30.2 +/- 3 vs 30.3 +/- 2.9 weeks). However, a greater number of patients had pregnancy prolonged beyond 7 days (42.1% vs 10.8% p = 0.005) and the mean latency period was significantly prolonged (11.4 +/- 18.8 vs 6.1 +/- 13.6 days, p = 0.001) in the piperacillin group compared with the control groups. CONCLUSIONS: Use of intravenous piperacillin for 72 hours in preterm premature rupture of membranes significantly prolongs the latency period between membrane rupture and delivery.

Adult↗
PubMed1993

Expression, identification and subcellular localization of the proteins encoded by the hepatitis C viral genome.

We have expressed the full-length coding region and selected domains of the hepatitis C virus (HCV) cDNA in mammalian cells by transfection. Using HCV antibody-positive human sera and monospecific antibodies the proteins encoded by the putative structural and non-structural regions of the open reading frame of HCV were identified as core (p22), E1 (gp32-35), E2 (gp68-72), NS2 (p23), NS3 (p72), NS4a and b (p10 and p27) and NS5a and b (p56 and p70). We have also defined the subcellular localizations of the HCV proteins using indirect immunofluorescence assays.

Animals↗
PubMed1993

Antibody response to core, envelope and nonstructural hepatitis C virus antigens: comparison of immunocompetent and immunosuppressed patients.

Some immunosuppressed patients with hepatitis C virus infection do not have detectable levels of antibody to hepatitis C virus on second-generation enzyme immunoassay. Antibodies to the envelope and nonstructural region 5 proteins have not been examined. Four groups of patients with hepatitis C virus infection were studied: (a) 20 immunocompetent patients, (b) 15 hemodialysis patients, (c) 17 kidney transplant recipients and (d) 3 acute leukemia patients who underwent bone marrow transplantation. Serum samples were tested for antibody to hepatitis C virus with a second-generation enzyme immunoassay and multi-antigen enzyme immunoassays and for hepatitis C virus RNA with a nested polymerase chain reaction assay. All the immunocompetent patients reacted to C25, C22 and C33C; 90% reacted to nonstructural region 5 antigen and 80% reacted to C100-3. Only 55% reacted against yeast-derived e1 and e2 antigens, but all reacted against vaccinia virus--expressed N e1 and e2 antigens, indicating that the envelope epitopes are conformational and glycosylated. Sixty-five percent to 90% of dialysis and kidney transplant patients reacted to C25, C22 and N e1 and e2, but only 12% to 60% reacted to C100-3, C33C and nonstructural region 5 antigen. Diminution or loss of reactivity to hepatitis C virus antigens was observed after kidney and bone marrow transplantation, with C25 and N e1 and e2 less affected. Our data suggest that incorporation of C25 and N e1 and e2 antigens in the assay for antibody to hepatitis C virus would improve the detection of hepatitis C virus infection in immunosuppressed patients.

Antibody Formation↗
PubMed1992

At least five related, but distinct, hepatitis C viral genotypes exist.

Hepatitis C virus, the major causative agent of blood-borne non-A, non-B hepatitis in the world, has been the subject of considerable nucleic acid sequence analysis. Although all reported hepatitis C sequences from the United States have been represented by the prototype hepatitis C virus type 1 sequence, two groups of variant sequences have been reported in Japan. However, we have noted five distinct, but related, genotypes (I-V) throughout the world, based on detailed sequence determination and analysis of the first 1700 nucleotides and part of the nonstructural region 5 at the C terminus of the open reading frame. The nucleotide sequence for a large number of hepatitis C virus isolates spanning six continents was obtained by direct sequence analysis of PCR products after reverse transcription. Genotype was classified by using several distinct sequence motifs. We observed that most genotypes coexist in several geographic regions, including the United States, Japan, Germany, and Italy. So far, genotype V has been found only in South Africa. Interestingly, each distinct genotype seems to be maintained throughout the genome in the segments studied. These genotype distinctions should be considered when designing specific diagnostic tests, developing potential vaccines, and studying viral transmission.

Amino Acid Sequence↗
PubMed1992

Improved detection of hepatitis C virus antibodies in high-risk populations.

Sera from 483 patients at high (group 1, n = 313) and lower (group 2, n = 170) risk for exposure to hepatitis C were tested for antibodies to hepatitis C using first-generation (c100-3) and second-generation enzyme-linked immunosorbent assays and four-antigen recombinant immunoblot assay. The second-generation enzyme-linked immunosorbent assay and nitrocellulose-based immunoblot assay differ from c100-3-based systems in the addition of expression products from the NS3/NS4 (c33c, c200) and putative nucleocapsid (c22-3) region of the hepatitis C genome. In group 1, the sensitivity of detection of hepatitis C antibodies was 45%, 55% and 46% by the first- and second-generation enzyme-linked immunosorbent assays and recombinant immunoblot assay, respectively. In group 2, antibodies were detected by each test system in 26%, 32% and 7% of patients, respectively. Most sera (99%) reactive with the first-generation enzyme-linked immunosorbent assay were reactive with the second-generation enzyme-linked immunosorbent assay (in group 1, 89% of these specimens demonstrated reactivity to at least one antigen with the immunoblot assay, compared with only 31% in group 2). An additional 12% (group 1) and 6% (group 2) of specimens demonstrated reactivity with the second-generation enzyme-linked immunosorbent assay only (of these, 75% [group 1] and 9% [group 2] demonstrated reactivity to at least one antigen with the immunoblot assay). Ninety-eight percent of specimens not reactive with both enzyme-linked immunosorbent assay test systems were also nonreactive by recombinant immunoblot assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗
PubMed1992

Comparative evaluation of supplemental hepatitis C virus antibody test systems.

Implementation of routine blood donor screening using anti-hepatitis C virus (HCV) enzyme immunoassay (EIA) has resulted in an urgent need for well-characterized supplemental assays to confirm the presence of HCV antibodies. A comparative study of four commercially available supplemental assays is reported here: first- and second-generation versions of a strip recombinant immunoblot assay (RIBA-1 and RIBA-2), an HCV neutralization EIA, and HCV neutralization plus synthetic peptide EIA. Three hundred sixty-seven blood donor specimens that were repeatedly reactive on HCV EIA were studied. Most specimens (93%) were also evaluated by radioimmunoassay (RIA) with a six-antigen panel, and 60 selected specimens were tested for HCV RNA by the polymerase chain reaction (PCR). RIBA-1 and RIBA-2 gave concordant results with 86 percent of specimens, while an additional 13 percent were correctly classified by RIBA-2 but not RIBA-1. Neutralization EIA alone correctly identified 94 percent of the study group, while the remaining 6 percent required the peptide EIA or the combined neutralization-peptide assay system for correct classification. The RIBA-2 and neutralization-peptide assay system for correct classification. The RIBA-2 and neutralization-peptide assay systems yielded identical results for 86 percent of specimens, and these results were supported by RIA and selected PCR testing. Only 2 specimens (0.5%) were frankly discrepant, while 51 specimens were indeterminate on either (47) or both (4) assays. When either the RIBA-2 or neutralization-peptide assay yielded an indeterminate interpretation, the other system correctly classified the specimen (based on concordance with RIA and PCR data) in a high proportion (92%) of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1992

Improved time-of-flight MR angiography of the brain with magnetization transfer contrast.

The authors hypothesized that magnetization transfer contrast (MTC) could be used to improve flow contrast in time-of-flight (TOF) magnetic resonance (MR) angiography. Two- and three-dimensional flow-compensated gradient-echo images were obtained with and without MTC. MTC images were obtained by applying low-power radio-frequency (RF) radiation with a frequency offset from the bulk "free" water resonance frequency before the excitation RF pulse. The signal intensity of stationary tissue decreased as the power applied for the MTC pulse was increased. A smaller decrease occurred in venous signal intensity as measured in the superior sagittal sinus, and less change was seen in the arterial signal intensity as measured in the middle cerebral artery. Cerebrospinal fluid showed no MTC effect. The use of MTC improved small-vessel depiction on maximum-intensity projection images. The authors conclude that use of MTC can substantially enhance the quality of TOF MR angiography of the brain.

Adult↗
PubMed1992

Fast magnetic resonance diffusion-weighted imaging of acute human stroke.

Rapid MRI of the molecular diffusion of water demonstrated cerebral infarcts in 32 patients. We studied these patients at various times following the onset of ischemic symptoms and found that diffusion-weighted imaging revealed the infarcts sooner than conventional T2-weighted spin-echo imaging did; four hyperacute infarcts were shown only by diffusion-weighted imaging. Acute infarcts had lower apparent diffusion coefficients (ADCs) than noninfarcted regions did. This relative difference in ADC reached a nadir in the first 24 hours and rose progressively thereafter. Chronic infarcts showed a relative increase in diffusion and were readily distinguishable from acute infarcts. The technique takes less than 2 minutes to apply using a standard 1.5-tesla scanner in the clinical setting. Diffusion-weighted imaging has the potential to play a role in improving the early anatomic diagnosis of stroke and therefore in the development and implementation of early stroke interventions.

Adult↗
PubMed1992

Image artifacts in fast magnetic resonance imaging.

Image artifacts are unwanted, spurious signal intensities that interfere with clinical diagnosis. This article gives an overview of image artifacts in magnetic resonance imaging. We discuss the causes of these artifacts, provide clinical examples, and offer solutions to avoid them.

Artifacts↗
PubMed1991

Reliable confirmation and quantitation of human immunodeficiency virus type 1 antibody using a recombinant-antigen immunoblot assay.

The recombinant DNA-derived, human immunodeficiency virus (HIV) antigen-based immunoblot assay (RIBA-HIV216) is a new supplemental (confirmatory) test developed to detect antibodies to HIV-1. The assay employs four recombinant viral antigens, corresponding to HIV-1 p24, p31, p41 and gp120 proteins, in an immunoblot format. With this assay, HIV-1 antigen reactivity was detected in all 683 infected patient serum or plasma specimens evaluated; 665 (97.6%) of these sera met the criteria for a positive interpretation, and 18 (2.6%) were classified as indeterminate. All 683 samples reacted with the recombinant gp41-equivalent protein. The first sequential enzyme immunoassay (EIA)-reactive samples collected from 33 seroconverting homosexual men reacted on RIBA-HIV216. Eleven (1.1%) of 999 EIA-negative blood donor sera reacted weakly with a single recombinant antigen (p24 or p31), whereas 13 to 48 percent had indeterminate reactions on viral lysate Western blots. One (1.5%) of 66 EIA-positive, Western blot-negative blood donor samples and 19 (29%) of 66 EIA-positive, Western blot-indeterminate blood donor samples scored indeterminate on RIBA-HIV216. Nonspecific reactivity was seen with only 1 (0.8%) of 114 patient sera containing possible interfering antibodies, whereas 33 percent of these samples had indeterminate reactions on Western blot and 35 percent had equivocal reactions on immunofluorescence assay (IFA). We conclude that the RIBA-HIV216 is approximately as sensitive as and significantly more specific than virus-derived Western blot and IFA. The RIBA-HIV216 also allows for semiquantitation of specific antibodies that may be of value in clinical staging and therapeutic monitoring.

Blotting, Western↗
PubMed1991

Fast time-of-flight MR angiography with improved background suppression.

A new technique for improving contrast in time-of-flight magnetic resonance (MR) angiography is described. A selective 180 degrees radio-frequency pulse was applied before data acquisition to suppress the signal intensity of stationary tissues. Vascular images were obtained in 1 second or less by using a single-shot, rapid gradient-echo sequence in conjunction with a very short echo time to minimize flow-related dephasing. Alternatively, the data acquisition could be divided into several segments that were combined to create an image. Because of the short imaging times, abdominal single-shot images were relatively insensitive to motion. The major drawback was decreased spatial resolution and limited signal-to-noise ratio. Spatial resolution of segmented flow images was comparable with that of standard gradient-echo images, but there was a marked reduction in the signal intensity of stationary tissues. For high-resolution MR angiography, the effective background suppression obtained by means of the segmented approach can improve the quality and reliability of images created by the maximum intensity projection algorithm.

Abdomen↗
PubMed1991

Fast selective black blood MR imaging.

To overcome the problems associated with gradient-echo (GRE) magnetic resonance (MR) angiography ("bright blood" imaging) and "black blood" imaging with presaturated spin-echo (SE) pulse sequences, the authors devised a new approach for black blood imaging. Their method, selective preinversion fast imaging with steady precession (turboFISP), uses a segmented GRE sequence for fast data acquisition. Nulling of vascular signal results, and stationary tissue appears bright. The method was compared with flow-compensated GRE imaging in a phantom and with GRE imaging and presaturated SE imaging in seven healthy volunteers and nine patients with various cardiac diseases. With phantoms, the selective preinversion turboFISP sequence produced better flow contrast than did GRE sequences. Selective preinversion turboFISP was often superior to SE imaging for depicting vessel lumina, particularly in patients with slowly flowing blood. Arteries appeared dark in selective black blood angiograms, but veins did not. Selective preinversion turboFISP can be used with bright blood GRE imaging to depict vessel lumina, and its capability for image acquisition within a breath hold and with cardiac gating minimizes artifacts from respiration and motion of the vessel wall.

Adult↗
PubMed1991

Ultrafast imaging using gradient echoes.

Ultrafast magnetic resonance (MR) imaging techniques can reduce scan times to less than 1 s. The rapid acquisition minimizes motion artifacts that have plagued MR studies of the heart and abdomen, and facilitates dynamic studies to observe physiological function. We first discuss fast gradient-echo methods, including various spoiled and steady-state gradient-echo techniques. Ultrafast methods are then considered, with the focus on turbo-fast low-angle shot (FLASH) (also known as snapshot or subsecond FLASH) imaging. Although turbo-FLASH is a subset of gradient echo methods, there are several distinguishing features. For instance, with T1- or T2-weighted turbo-FLASH, the magnetization never reaches a steady state, so that the phase encode order becomes an important imaging parameter. Furthermore, image contrast is obtained by adjusting the magnetization preparation module, which is independent of the data acquisition module that follows. The signal behavior and strategies for contrast optimization are discussed. Potential clinical applications, including perfusion imaging, cardiac cine, breath-hold abdominal imaging, angiography, diffusion imaging, and three-dimensional studies, are explored.

Fourier Analysis↗