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Biomedical subjects

P Y Chen

Publications and source records attributed to P Y Chen.

At least 19 recordsLinked to original sources

Depression and somatic symptoms within the farming community.

The relationship between somatic symptoms and depression was investigated in a population of farm operators and their spouses. The sample consisted of principal farm operators and their spouses from northeastern Colorado. There were a total of 709 participants who completed data relevant for our analyses. Exploratory and confirmatory factor analyses were conducted on the symptom inventory, and suggested a two-factor structure. One of the factors consisted of symptoms of a psychological nature, and the other consisted of physical symptoms. While both of the factors were significantly correlated with depression, the factor with psychological items was more strongly related to depression. Gender differences in the symptom factor structure were investigated, and only a few minor differences were found. Gender differences in relationships between the somatic symptom factors and depression were also investigated and were not found. Implications for farm operators, spouses, and rural healthcare providers were discussed.

Adult↗

Cardiac complications of enterovirus rhombencephalitis.

BACKGROUND: Epidemics of enterovirus 71 infection have caused the death of many children throughout the world. Rhombencephalitis, brain stem encephalitis, and heart failure were present in all of the fatal cases. However, no evidence of myocarditis was noted in the heart specimens, and the mechanism of heart failure remains unknown. AIMS: To characterise the presentation of cardiac complications in children with enterovirus rhombencephalitis and discuss its pathogenesis. METHODS: Ninety one consecutive patients with enterovirus rhombencephalitis underwent echocardiography. Of these, 17 patients (nine male, eight female; median age 14 months, range 4-57 months) with left ventricular dysfunction were studied. RESULTS: Tachycardia was noted in all patients and systemic hypertension in 12. Muscle-brain fraction of creatine kinase was >5% in 14 patients. Plasma norepinephrine and epinephrine levels were significantly raised in the three patients in whom these were analysed. Electrocardiographic abnormalities were noted in eight patients. Pulmonary oedema was complicated in 15 patients. The initial ejection fraction of the left ventricle was 22-58% (mean 37%, SD 11%). All patients deteriorated to hypotensive shock within 12 hours and 13 died. Heart specimens from seven patients showed no evidence of myocarditis, but significant coagulative myocytolysis, myofibrillar degeneration, and cardiomyocyte apoptosis were observed. CONCLUSIONS: Acute heart failure was noted in 19% of patients with enterovirus rhombencephalitis, which had a fatality rate of 77%. It was not caused by myocarditis but possibly by neurogenic cardiac damage.

Blood Pressure↗

The prevalence and spectrum of alpha and beta thalassaemia in Guangdong Province: implications for the future health burden and population screening.

AIM: Thalassaemia is a good candidate disease for control by preventive genetic programmes in developing countries. Accurate population frequency data are needed for planning the control of thalassaemia in the high risk Guangdong Province of southern China. METHODS: In total, 13397 consecutive samples from five geographical areas of Guangdong Province were analysed for both haematological and molecular parameters. RESULTS: There was a high prevalence of carriers of alpha thalassaemia (8.53%), beta thalassaemia (2.54%), and both alpha and beta thalassaemia (0.26%). Overall, 11.07% of the population in this area were heterozygous carriers of alpha and beta thalassaemia. The mutation spectrum of alpha and beta thalassaemia and its constitution were fully described in this area. This study reports the true prevalence of silent alpha thalassaemia in the southern China population for the first time. In addition, two novel mutations that give rise to alpha thalassaemia, one deletion resulting in beta thalassaemia, and a rare deletion (--(THAI) allele) previously unreported in mainland China were detected. The frequency of the most common mutation, the Southeast Asian type of deletion (--(SEA), accounting for 48.54% of all alpha thalassaemias) was similar to the total of two alpha(+) thalassaemia deletions (-alpha(3.7) and -alpha(4.2), accounting for 47.49% of alpha thalassaemia). CONCLUSION: Both alpha and beta thalassaemia are widely distributed in Guangdong Province of China. The knowledge gained in this study will enable the projected number of pregnancies at risk to be estimated and a screening strategy for control of thalassaemia to be designed in this area.

Adult↗

The use of high-dose-rate brachytherapy alone after lumpectomy in patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with early-stage breast cancer. METHODS AND MATERIALS: Thirty-seven patients with 38 Stage I-II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with (192)Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days. RESULTS: Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients. CONCLUSION: In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed.

Aged↗

Accelerated treatment of breast cancer.

PURPOSE: Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS: Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS: No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P =.31 and 2% v 1%, P =.63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P =.24), disease-free survival (87% v 91%, P =.55), overall survival (90% v 93%, P =.66), or cause-specific survival (97% v 99%, P =.28). CONCLUSION: Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.

Actuarial Analysis↗

Impact of boost technique on outcome in early-stage breast cancer patients treated with breast-conserving therapy.

We reviewed our institution's experience treating early-stage breast cancer patients with breast-conserving therapy (BCT) to determine the impact of boost technique on outcome. A total of 552 patients with stage I and II breast cancer were managed with BCT. All patients were treated with a partial mastectomy and radiation therapy (RT). RT consisted of 45 Gy to 50 Gy external beam irradiation to the whole breast followed by a boost to the tumor bed using either electrons (232 patients), photons (15 patients), or an interstitial implant (316 patients). Local control and cosmetic outcome was compared among three patient groups based on the type of boost used. Forty-one patients had a recurrence of cancer in the treated breast for 5-, 10-, and 13-year actuarial local recurrence rates of 2.8%, 7.5%, and 11.2%, respectively. There were no significant differences in the local recurrence rates or cosmetic outcome using electrons, photons, or an interstitial implant. On multivariate analysis, only young age and margin status were associated with local recurrence. Stage I and II breast cancer patients undergoing BCT can be effectively managed with electron, photon, or interstitial implant boost techniques. Long-term local control and cosmetic outcome are excellent regardless of which boost technique is used.

Adult↗

Intraocular lens implantation after penetrating keratoplasty.

PURPOSE: We evaluated the clinical results of nonsimultaneous penetrating keratoplasty, cataract extraction, and intraocular lens (IOL) implantation (two-stage surgery) for combined corneal disease and cataract. METHODS: Twenty-six eyes of 24 patients with an average age of 46 years who underwent two-stage surgery were studied retrospectively. Variables included visual acuity, refractive status, specular microscopy before and after IOL implantation (6 months), and the occurrence of graft failure. Astigmatism was corrected by suture removal and relaxing incision. The mean follow-up after IOL placement was 16 months. RESULTS: Unaided visual acuity was 20/100 or better in 22 (83%) eyes after the second procedure. Twenty-one (81%) eyes had an aided visual acuity of at least 20/40. The mean refractive and absolute errors were -1.49 +/- 1.39 diopters (D) and 1.55 +/- 1.30 D, respectively. The mean keratometric and refractive cylinders were 3.50 D and 2.26 D, respectively. Nineteen (73%) eyes had a spherical equivalent refraction within 2 D of emmetropia. Anisometropia (> or =3 D) occurred in four (15%) eyes. The endothelial cell density, the coefficient of variation, and the percentage of hexagonal cells documented by specular microscopy were not significantly different before and after IOL implantation. Complications included three rejections, two cases of herpetic recurrence, and one late decompensation. Two graft failures (8%) occurred after secondary surgery. CONCLUSION: The two-stage surgery is a safe and effective modality.

Adolescent↗

The role of a beta-bulge in the folding of the beta-hairpin structure in ubiquitin.

It is known that the peptide corresponding to the N-terminal beta-hairpin of ubiquitin, U(1-17), can populate the monomeric beta-hairpin conformation in aqueous solution. In this study, we show that the Gly-10 that forms the bulge of the beta-turn in this hairpin is very important to the stability of the hairpin. The deletion of this residue to desG10(1-16) unfolds the structure of the peptide in water. Even under denaturing conditions, this bulge appears to be important in maintaining the residual structure of ubiquitin, which involves tertiary interactions within the sequence 1 to 34 in the denatured state. We surmise that this residual structure functions as one of the nucleation centers in the folding process and is important in stabilizing the transition state. In accordance with this idea, deleting Gly-10 slows down the refolding and unfolding rate by about one half.

Amino Acid Substitution↗

Effects of turn residues in directing the formation of the beta-sheet and in the stability of the beta-sheet.

The designed peptide (denoted 20-mer, sequence VFITS(D)PGKTYTEV(D)PGOKILQ) has been shown to form a three-strand antiparallel beta-sheet. It is generally believed that the (D)Pro-Gly segment has the propensity to adopt a type II' beta-turn, thereby promoting the formation of this beta-sheet. Here, we replaced (D)Pro-Gly with Asp-Gly, which should favor a type I' turn, to examine the influence of different type of turns on the stability of the beta-sheet. Contrary to our expectation, the mutant peptide, denoted P6D, forms a five-residue type I turn plus a beta-bulge between the first two strands due to a one amino-acid frameshift in the hydrogen bonding network and side-chain inversion of the first beta-strand. In contrast, the same kind of substitution at (D)Pro-14 in the double mutant, denoted P6DP14D, does not yield the same effect. These observations suggest that the SDGK sequence disfavors the type I' conformation while the VDGO sequence favors a type I' turn, and that the frameshift in the first strand provides a way for the peptide to accommodate a disfavored turn sequence by protruding a bulge in the formation of the beta-hairpin. Thus, different types of turns can affect the stability of a beta-structure.

Amino Acid Sequence↗

Causal inference on the difference of the restricted mean lifetime between two groups.

When comparing survival times between two treatment groups, it may be more appropriate to compare the restricted mean lifetime, i.e., the expectation of lifetime restricted to a time L, rather than mean lifetime in order to accommodate censoring. When the treatments are not assigned to patients randomly, as in observational studies, we also need to account for treatment imbalances in confounding factors. In this article, we propose estimators for the difference of the restricted mean lifetime between two groups that account for treatment imbalances in prognostic factors assuming a proportional hazards relationship. Large-sample properties of our estimators based on martingale theory for counting processes are also derived. Simulation studies were conducted to compare these estimators and to assess the adequacy of the large-sample approximations. Our methods are also applied to an observational database of acute coronary syndrome patients from Duke University Medical Center to estimate the treatment effect on the restricted mean lifetime over 5 years.

Biometry↗

Preparation and use of a photoactivatable glucose-6-phosphate analogue.

A benzophenone-containing derivative of glucose-6-phosphate, 6-[(3-([2,3-3H2]-p-benzoyl dihydrocinnamidoylpropyl-1-oxy)phosphoryl]-D-glucopyranose ([3H]BZDC-Glc-6-P) was synthesized and employed to photoaffinity label proteins on intact rat liver microsomes. The use of a non-photoactivatable, UV-transparent desoxy analogue of BZDC, named p-benzyldihydrocinnamoyl (BnDC), is introduced as a general method to achieve competition when hydrophilic ligands are modified with hydrophobic photophores.

Animals↗

Improving the dosimetric coverage of interstitial high-dose-rate breast implants.

PURPOSE/OBJECTIVE: We performed a retrospective computed tomography (CT)-based three-dimensional (3D) dose-volume analysis of high-dose-rate (HDR) interstitial breast implants to evaluate the adequacy of lumpectomy cavity coverage, and then designed a simple, reproducible algorithm for dwell-time adjustment to correct for underdosage of the lumpectomy cavity. METHODS AND MATERIALS: Since March 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. In this protocol, all patients received 32 Gy in 8 fractions of 4 Gy over 4 days. Eleven patients treated with HDR brachytherapy who underwent CT scanning after implant placement were included in this analysis. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system, and the relevant tissue volumes were outlined on each axial slice. The implant dataset, including the dwell positions and dwell times, were imported into the 3D planning system and then registered to the visible implant template in the CT dataset. The calculated dose distribution was analyzed with respect to defined volumes via dose-volume histograms. Due to the variability of lumpectomy cavity coverage discovered in this 3D quality assurance analysis, dwell times at selected positions were adjusted in an attempt to improve dosimetric coverage of the lumpectomy cavity. Using implant data from 5 cases, a dwell-time adjustment algorithm was designed and was then tested on 11 cases. In this algorithm, a point P was identified using axial CT images, which was representative of the underdosed region within the cavity. The distance (d) from point P to the nearest dwell position was measured. A number of dwell positions (N) nearest to point P were selected for dwell time adjustment. The algorithm was tested by increasing the dwell times of a variable number of positions (N = 1, 3, 5, 7, 10, and 20) by a weighting factor (alpha), where alpha = f(d) and alpha > 1, and subsequently performing 3D dose-volume analysis to evaluate the improvement in lumpectomy cavity coverage. RESULTS: Before adjustment in the 11 implants, the median proportion of the lumpectomy cavity and target volume that received at least the prescription dose was 85% and 68%, respectively. After dwell-time adjustment, lumpectomy cavity coverage was significantly improved in all 11 cases. The median distance from point P to the nearest dwell position (d) was 1.4 cm (range 0.9-1.9). The median volume of the lumpectomy cavity receiving 32 Gy increased from 85.3% in the actual implant to 97.0% (range 74-100%) by increasing the dwell time of a single dwell position by a median factor (alpha) of 12.2 according to the above algorithm. With N = 3, the median proportion of the cavity volume receiving 32 Gy was improved to 97.5% (range 77-100%), with a median alpha of 5.7. Further improvement in lumpectomy cavity coverage was relatively small by increasing additional dwell times. In addition, with N = 20, the median absolute volume of breast tissue receiving 150% of the prescription dose was 70.3 cm3 compared to 26.3 cm3 in the actual implant; whereas with N = 1 or N = 3, this median volume was only 35.9 and 42.0 cm3, respectively. CONCLUSION: Lumpectomy cavity coverage sometimes appears suboptimal with interstitial HDR breast brachytherapy using our current technique. A simple dwell-time increase at only 1-3 dwell positions can compensate for some underdosage without creating significant regions of overdosage. Using simple methodology, a single reference point representing the underdosed region can be utilized for initial selection of the dwell positions to be increased.

Algorithms↗

A longitudinal study of relations between job stressors and job strains while controlling for prior negative affectivity and strains.

Interpretation of observed relations between job stressors and job strains in cross-sectional surveys is often ambiguous because of possible 3rd variables (both stable background factors, such as personality, and transitory occasion factors, such as mood). In this longitudinal study, negative affectivity (NA) and strains were assessed both in college and later on the job. Stressors were assessed only on the job. Evidence was found that some background factors affected measures of job stressors and job strains in that college measures were significantly related to subsequent measures on the job. Relations between job stressors and job strains, however, were in most cases not affected significantly when prior strains and NA were controlled for. Furthermore, the results suggested that NA measures are subject to occasion factors.

Adult↗

Trace Metals' abnormalities in hemodialysis patients: relationship with medications.

A multicenter collaborative study was performed to investigate the prevalence of abnormal blood contents of 6 trace metals, copper (Cu), zinc (Zn), aluminum (Al), lead (Pb), cadmium (Cd), and mercury (Hg), in hemodialysis (HD) patients and to analyze their relationship with the medications, such as CaCO3, Ca acetate, Al containing phosphate-binding agents, 1,25-dihydroxy vitD3, 1-hydroxy vitD3, and erythropoietin (EPO), as well as hematocrit level, by chi-square statistics. From 6 medical centers in Taiwan, we included 456 patients in maintenance HD for more than 4 months for this study, and they had continued the previously mentioned medications for at least 3 months. Blood samples were collected before initiating HD, and atomic absorption spectrophotometry was used to measure plasma levels of Cu, Zn, and Al as well as whole blood levels of Pb, Cd, and Hg. Three hundred seventy-five (78%) of the HD patients had low plasma Zn levels, that is, <800 microg/L, and the mean (+/-SD) concentration was 705.8 (+/-128.23) microg/L in all subjects. One hundred forty-one (31%) of the HD patients had high plasma Al, that is, >50 microg/L, and the mean (+/-SD) was 44.30 (+/-28.28) microg/L in all subjects. Three hundred thirty-three (73%) of the dialysis patients had high Cd levels, that is, >2.5 microg/L, and the mean (+/-SD) was 3.32 (+/-1.49) microg/L in all subjects. The majority of HD patients had normal blood levels of Cu, PB, and Hg. Only 21 (4. 6%), 5 (1.1%), and 3 (0.06%) patients had elevated blood levels of Cu, Pb, and Hg, respectively. Their mean (+/-SD) blood concentration of Cu, Pb, and Hg were 1,049.78 (+/-233.25) microg/L, 7.45 (+/-3.95) microg/dL, and 3.17 (+/-25.56) microg/L, respectively. Three patients had elevated plasma Hg concentrations, that is, 546, 12.6, and 24.0 microg/L, respectively. In the 152 normal healthy age and sex matched control group, the blood levels of Al, Cd, and Pb were all significantly lower than the HD patients. However, the levels of Cu and Zn were higher in the control group. The Hg level was not significantly different in both groups. There was no statistical difference between patients with normal and abnormal blood levels of trace metals in various medications except Al containing phosphate binder. The Al containing phosphate binder users had significantly higher plasma Al levels (54.71 +/- 26.70 versus 41.15 +/- 28.03 microg/L, p < 0.001) and hematocrit levels (29.61 +/- 4.61 versus 27. 81 +/- 3.91, p < 0.0005). There was no statistical correlation between erythropoietin (EPO) dose and hematocrit level in these patients. In conclusion, the blood level of trace metals of these HD patients except Al was not related to their medications. However, caution must be exercised in interpreting this result as dose and duration of medication; efficiency of HD and water treatment may play an important role. Otherwise, environmental factors, diet, and the aging process may contribute to the trace metal burden in uremia. Thus, Zn and Cu are abundant in seafood, and Cd is abundant in contaminated plants such as rice.

Acetates↗

Structural characterization of a mutant peptide derived from ubiquitin: implications for protein folding.

The formation of the N-terminal beta-hairpin of ubiquitin is thought to be an early event in the folding of this small protein. Previously, we have shown that a peptide corresponding to residues 1-17 of ubiquitin folds autonomously and is likely to have a native-like hairpin register. To investigate the causes of the stability of this fold, we have made mutations in the amino acids at the apex of the turn. We find that in a peptide where Thr9 is replaced by Asp, U(1-17)T9D, the native conformation is stabilized with respect to the wild-type sequence, so much so that we are able to characterize the structure of the mutant peptide fully by NMR spectroscopy. The data indicate that U(1-17)T9D peptide does indeed form a hairpin with a native-like register and a type I turn with a G1 beta-bulge, as in the full-length protein. The reason for the greater stability of the U(1-17)T9D mutant remains uncertain, but there are nuclear Overhauser effects between the side chains of Asp9 and Lys 11, which may indicate that a charge-charge interaction between these residues is responsible.

Amino Acid Sequence↗

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.

Aged↗