Biomedical subjects

M H Chen

Publications and source records attributed to M H Chen.

At least 73 records · Page 4Linked to original sources

PubMed1999

Monte Carlo EM for missing covariates in parametric regression models.

We propose a method for estimating parameters for general parametric regression models with an arbitrary number of missing covariates. We allow any pattern of missing data and assume that the missing data mechanism is ignorable throughout. When the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM algorithm by the method of weights proposed in Ibrahim (1990, Journal of the American Statistical Association 85, 765-769). We extend this method to continuous or mixed categorical and continuous covariates, and for arbitrary parametric regression models, by adapting a Monte Carlo version of the EM algorithm as discussed by Wei and Tanner (1990, Journal of the American Statistical Association 85, 699-704). In addition, we discuss the Gibbs sampler for sampling from the conditional distribution of the missing covariates given the observed data and show that the appropriate complete conditionals are log-concave. The log-concavity property of the conditional distributions will facilitate a straightforward implementation of the Gibbs sampler via the adaptive rejection algorithm of Gilks and Wild (1992, Applied Statistics 41, 337-348). We assume the model for the response given the covariates is an arbitrary parametric regression model, such as a generalized linear model, a parametric survival model, or a nonlinear model. We model the marginal distribution of the covariates as a product of one-dimensional conditional distributions. This allows us a great deal of flexibility in modeling the distribution of the covariates and reduces the number of nuisance parameters that are introduced in the E-step. We present examples involving both simulated and real data.

Algorithms↗

PubMed1999

Mutagenic analysis of the 3' cis-acting elements of the rubella virus genome.

Thermodynamically predicted secondary structure analysis of the 3'-terminal 305 nucleotides (nt) of the rubella virus (RUB) genome, a region conserved in all RUB defective interfering RNAs, revealed four stem-loop (SL) structures; SL1 and SL2 are both located in the E1 coding region, while SL3 and SL4 are within the 59-nt 3' untranslated region (UTR) preceding the poly(A) tract. SL2 is a structure shown to interact with human calreticulin (CAL), an autoantigen potentially involved in RUB RNA replication and pathogenesis. RNase mapping indicated that SL2 and SL3 are in equilibrium between two conformations, in the second of which the previously proposed CAL binding site in SL2, a U-U bulge, is not formed. Site-directed mutagenesis of the 3' UTR with a RUB infectious clone, Robo302, revealed that most of the 3' UTR is required for viral viability except for the 3'-terminal 5 nt and the poly(A) tract, although poly(A) was rapidly regenerated during subsequent replication. Maintenance of the overall SL3 structure, the 11-nt single-stranded sequence between SL3 and SL4, and the sequences forming SL4 were all important for viral viability. Studies on the interaction between host factors and the 3' UTR showed the formation of three RNA-protein complexes by gel mobility shift assay, and UV-induced cross-linking detected six host protein species, with molecular masses of 120, 80, 66, 55, 48, and 36 kDa, interacting with the 3' UTR. Site-directed mutagenesis of SL2 by nucleotide substitutions showed that maintenance of SL2 stem rather than the U-U bulge was critical in CAL binding since mutants having the U-U bulge base paired had a similar binding activity for CAL as the native structure whereas mutants having the SL2 stem destabilized had much lower binding activity. However, all of these mutations gave rise to viable viruses when introduced into Robo302, indicating that binding of CAL to SL2 is independent of viral viability.

Base Sequence↗

PubMed1999

Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer.

PURPOSE: To present nomograms providing estimates of prostate-specific antigen (PSA) failure-free survival after radical prostatectomy (RP) or external-beam radiation therapy (RT) for men diagnosed during the PSA era with clinically localized disease. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine the prognostic significance of the pretreatment PSA level, 1992 American Joint Committee on Cancer (AJCC) clinical stage, and biopsy Gleason score in predicting the time to posttherapy PSA failure in 1,654 men with T1c,2 prostate cancer managed with either RP or RT. RESULTS: Pretherapy PSA, AJCC clinical stage, and biopsy Gleason score were independent predictors (P < .0001) of time to posttherapy PSA failure in patients managed with either RP or RT. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in the format of a nomogram stratified by the pretreatment PSA, AJCC clinical stage, biopsy Gleason score, and local treatment modality. CONCLUSION: Men at high risk (> 50%) for early (< or = 2 years) PSA failure could be identified on the basis of the type of local therapy received and the clinical information obtained as part of the routine work-up for localized prostate cancer. Selection of these men for trials evaluating adjuvant systemic and improved local therapies may be justified.

Humans↗

PubMed1999

Long-term effects of in vivo angioplasty in normal and vasospastic canine carotid arteries: pharmacological and morphological analyses.

OBJECT: A canine model of hemorrhagic vasospasm of the high cervical internal carotid artery (ICA) was used to study the long-term effects of transluminal balloon angioplasty (TBA) on the structure and function of the arterial wall. METHODS: Forty dogs underwent surgical exposure of both distal cervical ICAs, followed by baseline angiographic studies on Day 0. Dogs in Group A (20 animals) underwent simple exposure of one ICA and placement of a silicone elastomer cuff around a segment of the opposite artery. These animals underwent repeated angiography on Day 7, and then TBA was performed on the uncuffed ICA; the cuff was removed from the opposite vessel. For dogs in Group B (20 animals), blood clot-filled cuffs were placed around both ICAs, and on Day 7 angiography was repeated and TBA was performed on one randomly selected ICA. Four animals were then killed from each group, and in the remaining animals the cuffs were removed from both ICAs. On Days 14, 21, 28, and 56, four animals from each group underwent repeated angiography and were then killed to permit pharmacological and morphological analyses of the ICAs. This protocol yielded five study categories: cuffed nonblood-coated arteries not subjected to TBA, blood-coated arteries not subjected to TBA, blood-coated arteries subjected to TBA, normal arteries subjected to TBA, and control arteries obtained from the proximal ICA in each animal. The contractile responses of isolated arterial rings obtained from each ICA were recorded after treatment with potassium chloride, noradrenaline, and serotonin, whereas relaxations in response to the calcium ionophore A23187 and papaverine were recorded after tonic contraction to noradrenaline had been established. Morphological analysis was performed using scanning electron microscopy. Arteries surrounded by an empty cuff exhibited no angiographic, pharmacological, or morphological differences compared with normal arteries on any study day. Arteries surrounded by blood developed angiographically confirmed vasospasm on Day 7, with characteristic pharmacological and morphological features; resolution of these symptoms occurred by Day 21. Vasospastic arteries subjected to TBA on Day 7 remained dilated on angiographic studies, exhibited impaired responses to pharmacological agents (except for papaverine), and showed altered morphological features until Day 28. Normal arteries subjected to TBA on Day 7 remained dilated on angiographic studies, exhibited impaired responses to pharmacological agents (except for papaverine), and displayed altered morphological features until Day 14. CONCLUSIONS: These results indicate that the canine high cervical ICA model produces consistent and reproducible vasospasm that follows a similar time course to that seen in humans. When TBA is performed in vasospastic arteries, it results in an immediate functional impairment of vascular smooth muscle that lasts for 2 weeks, with resolution at 3 weeks; morphological changes are mostly resolved 3 weeks post-TBA. In normal vessels, TBA causes functional impairment and morphological alterations that are not as severe or as long-lasting as those seen in vasospastic arteries.

Angioplasty, Balloon↗

PubMed1999

Syntheses and biological activities of chiral piperidines-tachykinin NK3 antagonists.

AIM: To develop nonpeptide tachykinin NK3 antagonists. METHODS: Five tachykinin NK3 antagonists were synthesized. Receptor binding assay and oral absorption study were made. RESULTS: The 4,4-disubstituted piperidine compounds (1b, 1c, and 1d) showed stronger activities (IC50 = 5.9, 6.2, and 11 nmol.L-1, respectively) than the monosubstituted ring compound 1e (IC50 = 17 nmol.L-1). 4-Phenyl (1b) and 4-phenylsulfonylmethyl (1c) compounds were more active than the 4-fluorobenzyl compound (1d). All antagonists were found to be orally absorbable, the T1/2 of 1b (6.4 h) was more than three-fold longer than that of 1a (1.9 h). CONCLUSION: Compound 1b had the best binding activity (IC50 = 5.9 nmol.L-1) and the best AUC (2081 micrograms.h.L-1).

Animals↗

PubMed1999

Combination of color Doppler ultrasonography and ultrasound-guided fine-needle aspiration cytology for localization of parathyroid lesions.

We examined the usefulness of color Doppler ultrasonography combined with ultrasound-guided fine-needle aspiration cytology (FNAC) for preoperative localization of parathyroid lesions in patients with hyperparathyroidism. Twenty-eight patients (19 men, 9 women; mean age, 56 years) with clinical and laboratory evidence of hyperparathyroidism underwent preoperative color Doppler ultrasonography and ultrasound-guided FNAC prior to surgery. On ultrasonography, the parathyroid lesions were anechoic or hypoechoic, located behind or at the margin of the thyroid gland, and mimicked blood vessels in some cases. On color Doppler ultrasound, parathyroid lesions showed little or no vascularity. They were easily differentiated from blood vessels, thus improving the safety of ultrasound-guided FNAC. Thirty-four (76%) of 45 surgically confirmed parathyroid lesions were detected with ultrasonography in 21 (75%) of the patients. There was no significant difference in the detection rates of lesions in the right upper, right lower, left upper, and left lower parathyroid glands. Eight (29%) patients had coexisting thyroid lesions. FNAC of the ultrasound-detected abnormalities provided preoperative confirmation that they were parathyroid lesions. In conclusion, our findings show that color Doppler ultrasonogrphy in combination with ultrasound-guided FNAC is useful for preoperative localization of parathyroid lesions.

Biopsy, Needle↗

PubMed1998

Analyzing outcome-based staging for clinically localized adenocarcinoma of the prostate.

BACKGROUND: A clinical staging system based on the prostate-specific antigen (PSA) and the calculated prostate carcinoma volume (cVCa) construct previously has been proposed. This study was performed to assess whether this proposed clinical staging system was valid in an independent surgical and radiation data set in patients with clinically localized disease. METHODS: Cox regression multivariable analyses were used to assess the significance of staging systems (1992 American Joint Commission on Cancer Staging [AJCC] clinical and pathologic stage, versus cVCa-PSA clinical stage) to predict time to posttherapy PSA failure in 441 and 465 patients managed by surgery and radiation, respectively. Significant staging systems identified using Cox regression were tested further using established comparative measures to define the most clinically useful system. RESULTS: Both the 1992 AJCC pathologic stage and the cVCa-PSA clinical stage were significant predictors of time to postoperative PSA failure (P = 0.0001), whereas only the cVCa-PSA clinical stage was a significant predictor of time to postradiation PSA failure (P = 0.0001) using a Cox regression multivariable analysis. Further analyses using a pairwise comparison of the 1992 AJCC pathologic stage and cVCa-PSA clinical stage found the cVCa-PSA staging system provided a more clinically useful prediction of time to postoperative PSA failure. Specifically, the cVCa-PSA staging system was able to identify surgically managed patients with pathologic AJCC T2 disease who did poorly (3-year bNED = 22%) while also selecting patients with clinical AJCC T2b,c disease that was managed by radiation who did well (3-year bNED = 100%). CONCLUSIONS: A clinical staging system based on parameters obtained during the routine evaluation for AJCC clinical T1,2 prostate carcinoma provided a clinically useful stratification of both postoperative and postradiation PSA failure free survival.

Adenocarcinoma↗

PubMed1998

Assessment of outcome prediction models for patients with localized prostate carcinoma managed with radical prostatectomy or external beam radiation therapy.

BACKGROUND: A clinical staging system for localized prostate carcinoma that provides reliable information on which management decisions regarding an individual patient can be based is lacking. This study compared the abilities of all published proposed clinical staging systems to predict time to prostate specific antigen (PSA) failure after radical prostatectomy or external beam radiation therapy for clinically localized prostate carcinoma. METHODS: A total of 1441 clinically localized prostate carcinoma patients who were managed with radical prostatectomy at the University of Pennsylvania in Philadelphia (n = 688) or the Brigham and Women's Hospital in Boston (n = 288) or with external beam radiation therapy at the Joint Center for Radiation Therapy in Boston (n = 465) were entered into this study. Patients who received adjuvant or neoadjuvant hormonal or radiation therapy were excluded. Akaike's Information Criterion (AIC) and Schwartz Bayesian Criterion (SBC) estimates, which are comparative measures, were calculated for each clinical staging system. Pairwise comparisons of the AIC and SBC estimates for the most predictive clinical staging systems were performed using a formal bootstrap technique with 2000 replications. RESULTS: Both the staging system based on the risk score and the staging system based on the calculated volume of prostate carcinoma and PSA (cVCa-PSA) optimized the prediction of time to posttreatment PSA failure. The cVCa-PSA system, however, provided a more clinically useful stratification of outcome. CONCLUSIONS: Improved clinical staging for patients with localized prostate carcinoma may be possible with parameters obtained during routine evaluation. Validation by other investigators is underway.

Aged↗

PubMed1998

Hepatitis C virus variants circumventing cytotoxic T lymphocyte activity as a mechanism of chronicity.

BACKGROUND & AIMS: High rate of chronicity after acute hepatitis C virus (HCV) infection cannot be explained in the presence of a multispecific cytotoxic T lymphocyte (CTL) response. The aim of this study was to investigate the effect of virus variants on CTL activity in patients in whom chronicity developed. METHODS: CTL clones specific to a decapeptide epitope derived from hypervariable region 1 were generated from 5 HLA-A2-positive patients with acute hepatitis C by in vitro stimulation with synthetic peptides. The sequential change of this CTL epitope and its influence on the CTL recognition were examined. RESULTS: Virus variants did not appear in 3 patients with recovery, whereas variants with altered peptide ligands capable of antagonizing CTL activity emerged rapidly in the remaining 2 patients in whom chronicity developed. Importantly, these HLA-A2-restricted, hypervariable region 1-specific CTL clones shared the use of T-cell receptor (TCR) genes AV6 and BV17. CONCLUSIONS: These data suggest that there is only a narrow T-cell repertoire responding to a single viral peptide/HLA ligand. The emergence of HCV variants with altered peptide ligands as TCR antagonists accompanied by a limited TCR repertoire may provide a mechanism for HCV chronicity.

Acute Disease↗

PubMed1998

A low rate of reinfection following effective therapy against Helicobacter pylori in a developing nation (China).

BACKGROUND & AIMS: In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. The aim of this study was to determine the rate of reinfection and ulcer recurrence in Chinese patients cured of H. pylori and duodenal ulcer disease. METHODS: One hundred eighty-four patients with duodenal ulcer disease shown by endoscopic examination (1 month) and 14C-urea breath test (3 months) after termination of treatment to have cleared their H. pylori were investigated. Patients were followed up by endoscopy (12 and 24 months) and breath test (6, 9, 12, 18, and 24 months). H. pylori status at endoscopic examination was determined by rapid urease, histology, and culture. In reinfected patients, random amplification of polymorphic DNA fingerprinting was used to compare isolates before and after therapy. RESULTS: Four patients were reinfected with H. pylori over 24 months (3 within 6 months and 1 at 24 months; average annual recurrence rate, 1.08%). Fingerprinting of isolates from 3 patients showed 1 patient (6 months) to have identical strains and the remainder to have nonidentical strains before and after treatment. Ulcer relapse occurred in 6 patients (4 H. pylori positive). CONCLUSIONS: Reinfection with H. pylori is rare in developing countries where treatment is effective.

Adult↗

PubMed1998

Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload.

OBJECTIVES: To identify gender differences in left ventricular remodeling, hypertrophy, and function in response to pressure overload due to ascending aortic banding in rats. BACKGROUND: Gender may influence the adaptation to pressure overload, as women with aortic stenosis have greater degrees of left ventricular hypertrophy and better left ventricular function than men. METHODS: Fifty-two weanling rats underwent ascending aortic banding (16 males, 18 females), or sham surgery (9 males, 9 females). At 6 and 20 weeks, rats underwent transthoracic echo Doppler studies, and closed-chest left ventricular pressures with direct left ventricular puncture. Perfusion-fixed tissues from eight rats were examined morphometrically for myocyte cross-sectional area and percent collagen volume. RESULTS: At 6 weeks after aortic banding, left ventricular remodeling, extent of hypertrophy, and function appeared similar in male and female rats. At 20 weeks, male but not female rats showed an early transition to heart failure, with onset of cavity dilatation (left ventricular diameter=155% vs. 121% of same-sex sham), loss of concentric remodeling (relative wall thickness=102% vs. 139% of sham), elevated wall stress (systolic stress=266% vs. 154% of sham), and diastolic dysfunction (deceleration of rapid filling=251% vs. 190% of sham). Left ventricular systolic pressures were higher in female compared with male rats (186+/-20 vs. 139+/-13 mm Hg), while diastolic pressures tended to be lower (14+/-4 vs. 17+/-4 mm Hg). CONCLUSIONS: Gender significantly influences the evolution of the early response to pressure overload, including the transition to heart failure in rats with aortic stenosis.

Adaptation, Physiological↗

PubMed1998

Laparoscopically assisted abdominal aortic aneurysm repair: first 20 cases.

PURPOSE: Laparoscopic surgery decreases postoperative pain, shortens hospital stay, and returns patients to full functional status more quickly than open surgery for a variety of surgical procedures. This study was undertaken to evaluate laparoscopic techniques for application to abdominal aortic aneurysm (AAA) repair. METHODS: Twenty patients who had AAAs that required a tube graft underwent laparoscopically assisted AAA repair. The procedure consisted of transperitoneal laparoscopic dissection of the aneurysm neck and iliac vessels. A standard endoaneurysmorrhaphy was then performed through a minilaparotomy using the port sites for the aortic and iliac clamps. Data included operative times, duration of nasogastric suction, intensive care unit days, and postoperative hospital days. Pulmonary artery catheters and transesophageal echocardiography were used in seven patients. For these patients data included heart rate, pulmonary artery systolic and diastolic pressures, mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, and end diastolic area. Data were obtained before induction, during and after insufflation, during aortic cross-clamp, and at the end of the procedure. RESULTS: Laparoscopically assisted AAA repair was completed in 18 of 20 patients. Laparoscopic and total operative times were 1.44 +/- 0.44 and 4.1 +/- 0.92 hours, respectively. Duration of nasogastric suction was 1.3 +/- 0.7 days. Intensive care unit stay was 2.2 +/- 0.9 days. The mean length of hospital stay was 5.8 days excluding three patients who underwent other procedures. There were two minor complications, one major complication (colectomy after colon ischemia), and no deaths. For the eight patients who had intraoperative transesophageal echocardiographic monitoring, no changes were noted in heart rate, pulmonary artery systolic pressure, pulmonary capillary wedge pressure, and cardiac index. Pulmonary artery diastolic pressure and central venous pressure were greatest during insufflation without changes in end-diastolic area. Volume status, as reflected by end-diastolic area and pulmonary capillary wedge pressure, did not change. CONCLUSIONS: Laparoscopically assisted AAA repair is technically challenging but feasible. Potential advantages may be early removal of nasogastric suction, shorter intensive care unit and hospital stays, and prompt return to full functional status. The hemodynamic data obtained from the pulmonary artery catheter and transesophageal echocardiogram during pneumoperitoneum suggest that transesophageal echocardiography may be sufficient for evaluation of volume status along with the added benefit of detection of regional wall motion abnormalities and aortic insufficiency. Further refinement in technique and instrumentation will make total laparoscopic AAA repair a reality.

Aged↗

PubMed1998

The significance of locating and filling the canal isthmus in multiple root canal systems. A scanning electron microscopy study of the mesiobuccal root of maxillary first permanent molars.

The mesiobuccal (MB) roots of 50 randomly selected maxillary first permanent molars were examined to evaluate the different configurations of canal isthmus and their incidences. Sections of the roots at 3.4, and 5 mm from the apex were prepared, acid etched, washed and dried. The apical side of each section was sputter coated with gold, examined by a Hitachi S-2500 scanning electron microscope and photographed. 36% of the mesiobuccal roots had one canal, whereas 64% had two canals. In the roots with two canals 31.25% contained either a complete isthmus, or accessory canals between the two main canals 31.25% showed partial isthmus formation. The significance of the different configurations is discussed. Our present findings indicate that the mesiobuccal roots of maxillary first permanent molars exhibit complex anatomy. Prudent judgement is essential in the canal isthmus preparation so that operators must provide meticulous skill and care to the patients.

Dental Pulp Cavity↗

PubMed1998

Differential inducibilities of GFAP expression, cytostasis and apoptosis in primary cultures of human astrocytic tumours.

Glial fibrillary acidic protein (GFAP) is an astrocytic lineage-specific intermediate filament protein, and its expression or non-expression is inversely correlated with the tumourigenecity of astrocytoma cells. To estimate the GFAP levels of astrocytes in intracranial tumour tissues, we established primary cultures from six astrocytic tumour specimens and used a double-staining flow cytometric method to detect the different levels of GFAP among these primary cultures. Although these primary cultures exhibited the same Matrigel invasiveness, their GFAP expression is inversely related to the rate of cell growth and the histologic grade of the original tumour. Phenylacetate, 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate, which are potent inducers of differentiation in various cancer cells, have been examined for their effects on these primary cultures. Cytostasis was more or less caused by these compounds in all six primary cultures, but induction of GFAP was observed only in the primary culture derived from a less malignant astrocytoma specimen having the highest intrinsic GFAP level. Interestingly, this primary culture, but not others, also exhibited increased HRG-alpha expression after phenylacetate or sodium butyrate treatment. Loss of the inducibility of differentiation-related gene expression could be one of the events involved in the malignant progression of astrocytomas. In addition, the chemotherapeutic agent BiCNU has a killing effect on all six primary culture cells, with LD50 less than 60 nM. The underlying mechanism was through the induction of apoptosis in these primary culture cells regardless of their varying malignancies of original tumours. However, unlike colon cancer and leukaemia cells, sodium butyrate could not induce apoptosis within 4 days in these astrocytic tumour cells, indicating that the cell context of different cell types indeed determined the ability of sodium butyrate to induce apoptosis.

Journal Article↗

PubMed1998

On the ultrastructure of softened cartilage: a possible model for structural transformation.

The fibrillar architecture in the general matrix of softened cartilage has been compared with that of the normal matrix using both Nomarski light microscopy and transmission electron microscopy with combined stereoscopic reconstruction. A pseudorandom network developed from an overall radial arrangement of collagen fibrils is the most fundamental ultrastructural characteristic of the normal general matrix. This, in turn, provides an efficient entrapment system for the swelling proteoglycans. Conversely, the most distinctive feature of the softened matrix is the presence of parallel and relatively unentwined fibrils, strongly aligned in the radial direction. The presence of an optically resolvable fibrous texture in the softened cartilage matrix indicates the presence of discrete bundles of closely packed and aligned fibrils at the ultrastructural level of organisation. The general absence of such texture in the normal cartilage general matrix is consistent with the much greater degree of interconnectedness and related short-range obliquity in the fibrillar architecture, hence the importance of the term pseudorandom network. A mechanism of structural transformation is proposed based on the important property of lateral interconnectivity in the fibrils which involves both entwinement and nonentwinement based interactions. The previously reported difference in intrinsic mechanical strength between the normal and softened matrices is consistent with the transformation model proposed in this study.

Aging↗

PubMed1998

The combination of preoperative prostate specific antigen and postoperative pathological findings to predict prostate specific antigen outcome in clinically localized prostate cancer.

PURPOSE: The independent clinical and pathological predictors of time to postoperative prostate specific antigen (PSA) failure were used to identify prostate cancer patients at high risk for this end point. MATERIALS AND METHODS: A Cox regression multivariate analysis was used to determine the prognostic significance of preoperative PSA, pathological stage, prostatectomy Gleason score and margin status in predicting the time to postoperative PSA failure in 862 men with palpable (T2) or PSA detected (T1c) prostate cancer. The 2-year PSA failure rates with 95% confidence intervals were calculated using the results of Cox regression analysis and a bootstrap procedure with 2,000 replications, respectively, and are presented in nomogram format stratified by preoperative PSA, pathological stage, prostatectomy Gleason score and margin status. RESULTS: Preoperative PSA (p = 0.0001), pathological stage (p< or =0.002), margin status (p = 0.0001) and prostatectomy Gleason score (p = 0.034) were independent predictors of time to postoperative PSA failure. CONCLUSIONS: Patients at high risk for early PSA failure could be identified postoperatively on the basis of preoperative PSA and prostatectomy pathology. Adjuvant therapy trials in these select patients may be justified.

Follow-Up Studies↗

PubMed1998

De novo unbalanced translocation resulting in monosomy for proximal 14q and distal 4p in a fetus with intrauterine growth retardation, Wolf-Hirschhorn syndrome, hypertrophic cardiomyopathy, and partial hemihypoplasia.

We present the perinatal findings of a fetus with a de novo unbalanced chromosome translocation that resulted in monosomy for proximal 14q and monosomy for distal 4p. Prenatal sonographic examination at 27 weeks of gestation showed intrauterine growth retardation, microcephaly, cardiomegaly with arrhythmia, and asymmetry of the upper limbs. Genetic amniocentesis showed an abnormal karyotype of 45,XX,der(4)t(4;14)(p16.3;q12),-14. Linkage analysis of the family confirmed the maternal origin of the deletions. Molecular refinement of the deletion breakpoints indicated that the breakpoints at 4p16.3 and 14q12 were located between loci D4S403 (present) and D4S394 (absent), and between loci D14S252 (present) and D14S64 (absent), respectively. Necropsy showed dysmorphic features compatible with Wolf-Hirschhorn syndrome, hypertrophic cardiomyopathy, partial hemihypoplasia, and a normal brain without evidence of holoprosencephaly. Our case adds to the list of clinical phenotypes associated with the proximal regions of 14q.

Abnormalities, Multiple↗

PubMed1998

[Decrease of cAMP and increase of amino acids contents in mouse brain after dihydroetorphine tolerance].

AIM: To study the mechanism of dihydroetorphine (DHE) tolerance. METHODS: DHE tolerance was produced by repeated s.c. injections in progressively increased doses to mice for 8 d. The concentrations of amino acids and cAMP were detected by RP-HPLC/fluorescence assay and radioimmunoassay, respectively. RESULTS: The basal contents of glutamic acid (Glu), aspartic acid (Asp), and GABA in whole brain (cerebellum removed) were increased respectively from 14.1 +/- 2.1, 3.0 +/- 0.4, and 1.8 +/- 0.8 mumol/g tissue in control mice to 17.2 +/- 2.2, 4.1 +/- 0.6, and 3.2 +/- 1.0 mumol/g tissue in tolerant mice, and the rates of increase were 22.0% (P < 0.05), 36.7% (P < 0.01), and 77.8% (P < 0.05 vs control), respectively. There was no significant difference in the basal contents of Gln (5.1 +/- 1.0 vs 4.5 +/- 1.7 mumol/g tissue of control). The basal contents of cAMP in hypothalamus and striatum were decreased respectively from 271 +/- 38 and 189 +/- 31 nmol/g tissue in control mice to 96 +/- 15 and 65 +/- 21 nmol/g tissue in tolerant mice (P < 0.01), and the rates of decrease were 64.6% and 65.6%, respectively. There was no significant difference of cAMP in cerebral cortex (72 +/- 20 vs 55 +/- 15 nmol/g tissue of control). CONCLUSION: The increases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypothalamus and striatum were involved in DHE tolerance.

Amino Acids↗