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T C Hsu

Publications and source records attributed to T C Hsu.

At least 37 records · Page 2Linked to original sources

Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers.

The interaction between environmental exposures and host susceptibility may lead to specific mutational events within head and neck squamous cell carcinoma (HNSCC). Furthermore, this interplay may determine not only the probability of cancer development but also the biologic characteristics of the tumor once it occurs. To better understand the relationship of mutagen sensitivity and tobacco and/or alcohol consumption on HNSCC carcinogenesis, we examined loss of heterozygosity on chromosome 3p in 58 HNSCCs using 10 microsatellite markers. Mutagen sensitivity was determined in vitro by quantitating bleomycin-induced chromatid breaks utilizing peripheral blood lympocytes from respective patients. Forty-six of the 58 invasive cancers showed allelic loss at one or more loci. Consistent with previous investigations, three discrete regions of deletions were identified: 3p13-14.2, 3p21.1-21. 2, and 3p25.1-26.1. The frequency and types of deletions were dependent upon tobacco and alcohol exposures. The distal region of 3p but not the remaining two regions was most frequently influenced by tobacco exposure. In contrast, heavy alcohol use when combined with tobacco use was associated with whole-arm loss of 3p rather than identifiable site-specific damage. Furthermore, this combined influence of alcohol and tobacco exposures on whole-arm loss was most apparent in those patients who expressed mutagen-sensitivity; the odds ratio of whole-arm loss increasing from 2.67 (95% CI 0. 21-33.49) in those individuals who were mutagen resistant to 13.5 (95% CI 1.3-136.0; P = 0.02 by Fisher's exact test) in those who were mutagen sensitive. An assessment of clinical parameters in this population demonstrated that patients with whole-arm loss were more likely to present with cervical lymph node metastases and advanced stage disease than patients with partial losses. Results indicate that various environmental exposures as well as the expression of mutagen sensitivity will influence the types of chromosome 3p allelic losses in head and neck cancers as well as the behavior of disease once it develops.

Alleles↗

Environmental tobacco smoking, mutagen sensitivity, and head and neck squamous cell carcinoma.

Although active tobacco smoking has been considered a major risk factor for head and neck cancer, few studies have evaluated environmental tobacco smoke (ETS) and its interaction with mutagen sensitivity on the risk of head and neck cancer. We investigated the relationship between ETS and head and neck cancer in a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. A structured questionnaire was used to collect ETS exposure and other covariates including a history of active tobacco smoking and alcohol use. ETS measures include a history of ETS exposure at home and at workplace. The associations between passive smoking and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Additive and multiplicative models were used to evaluate effect modifications between ETS and mutagen sensitivity. The crude odds ratio (OR) for ETS exposure was 2.8 [95% confidence intervals (CI), 1.3-6.0]. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and marijuana use, the risk of squamous cell carcinoma of the head and neck was increased with ETS (adjusted OR, 2.4; 95% CI, 0.9-6.8). Dose-response relationships were observed for the degree of ETS exposure; the adjusted ORs were 2.1 (95% CI, 0.7-6.1) for those with moderate exposure and 3.6 (95% CI, 1.1-11.5) for individuals with heavy exposure (P for trend = 0.025), in comparison with those who never had ETS exposures. These associations and the dose-response relationships were still present when the analysis was restricted to nonactive smoking cases and controls (crude OR, 2.2; 95% CI, 0.6-8.4). Crude odds ratios were 1.8 for those with moderate ETS exposure and 4.3 for individuals with heavy ETS exposure among nonsmoking cases and controls (P for trend = 0.008). More than multiplicative interaction was suggested between passive smoking and mutagen sensitivity. This study suggests that ETS exposure may increase the risk of head and neck cancer with a dose-response pattern. Our analysis indicated that passive smoking may interact with mutagen sensitivity and other risk factors to increase the risk of head and neck cancer. Our results need to be interpreted with caution because of potential residual confounding effects of active tobacco smoking and other methodological limitations. Future large-scale studies are warranted to confirm our findings.

Adult↗

Is total knee replacement more painful than total hip replacement?

BACKGROUND: During its use in pain management the patient-controlled analgesia (PCA) devices are capable of registering the course of treatment at patient request, the condition of drug delivery and total amount of drug being given. The patients could determine the need of medication to their own satisfaction while forced treatment by the bias of the health care personnel is avoided and the safety of patients is further warranted. In pain relief with this device, the number of requests for analgesia and the dose of analgesic used can be easily measured. Therefore, it is more objective to compare the pain intensity among different types of operation when PCA device is used. Using PCA morphine consumption as a parameter, we attempted to elucidate the difference of intensity of pain associated with total hip and total knee replacements by comparing their morphine requirement. METHODS: In this prospective cohort study, 50 patients who underwent either total hip replacement (THR, n = 24) or total knee replacement (TKR, n = 26) were enrolled. After recovery from general anesthesia when the patients first complained intense pain in the recovery room, morphine was given intravenously in titration with a calculated loading dose in 30 min to achieve an acceptable analgesia (VAS < or = 3) followed by morphine PCA at 1 mg bolus with a lockout interval of 6 min. The patients were then followed for 48 h. During and at the end of the course the data relevant to pain score, total dose, demand, delivery, and adverse effects were recorded for assessment. RESULTS: With the use of PCA, the pain scores were similar in both surgical groups in the 48 h observation. Total consumption of morphine in THR was 13.2 +/- 8.1 mg as against 19.7 +/- 5.7 mg in TKR in postoperative day 1 and 25.2 +/- 12.7 mg as against 34.1 +/- 13.9 mg in postoperative day 2 (P < 0.05, t-test). Demand/delivery ratio was not statistically significant between the 2 groups at 24 and 48 h (t-test). Minor adverse effects were seen in both groups but the differences were not significant. CONCLUSIONS: Using PCA morphine consumption as parameter, we can distinguish the magnitude of pain intensity between 2 major orthopedic surgeries. The deeper and more extensive operation would in total hip replacement does not mean that it is a more painful procedure than total knee replacement. Several speculations are proposed.

Aged↗

Family history of cancer, mutagen sensitivity, and increased risk of head and neck cancer.

To evaluate individual cancer susceptibility, 170 previously untreated patients with pathologically-confirmed squamous cell carcinoma of the oral cavity, pharynx, and larynx, and 175 age- and sex-matched health controls were investigated for the occurrence of cancer in first-degree relatives along with other established risk factors for head and neck cancer. More than 54% of these subjects were assayed for mutagen sensitivity by quantifying in-vitro bleomycin-induced chromosomal breaks within peripheral blood lymphocytes. After adjusting for age, gender, education, family income, tobacco and alcohol consumption, the odds ratio associated with three or more first-degree relatives with cancer at any site was 3.79 (95% CI 0.9-15.9) with a linearly-increased trend in risk (P = 0.040). Significantly elevated risk was found to be associated with a history of cancer within siblings (OR = 2.61, 1.2-5.6, P = 0.014). Patients with a family cancer history and mutagen sensitivity were at greatest risk (OR = 7.88, 2.5-25.3, P = 0.005), indicating an additive interactive effect. The findings suggested that genetic familial influence is important in the causation of head and neck cancer.

Aged↗

Ultrasonographic measurement of the mechanical properties of the sole under the metatarsal heads.

The sole under the metatarsal heads functions as a shock absorber during walking and running. The mechanical properties of the sole provide the primary defense against the development of metatarsalgia and foot ulceration. However, limited information about these properties has been documented. In this study, we used ultrasonography to evaluate the mechanical properties, including unloaded thickness, compressibility index, elastic modulus, and energy dissipation ratio, of the sole in 20 healthy subjects. The unloaded thickness decreased progressively from the first to the fifth metatarsal heads, with values of 1.50, 1.36, 1.25, 1.14, and 1.04 cm. The sole under the first metatarsal head had the greatest values for the compressibility index and elastic modulus (55.9% and 1.39 kg/cm2), and the sole under the third metatarsal head had the smallest values (50.8% and 1.23 kg/cm2). The sole under the fifth metatarsal head had the greatest energy dissipation ratio (33.7%), followed by that under the third, second, first, and fourth metatarsal heads. Multivariate adjusted linear regression showed that the unloaded thickness, compressibility index, and elastic modulus values increased significantly with age and body weight (p < 0.05) and that the energy dissipation ratio increased significantly with body weight (p < 0.05)

Adolescent↗

Correlation of clinical and ultrasonographic features in congenital muscular torticollis.

OBJECTIVE: To find the relationship between the ultrasonographic pictures and the clinical features of patients with congenital muscular torticollis (CMT). DESIGN: Prospective survey of patients with clinically suspected CMT by high-resolution ultrasonography. SETTING: Rehabilitation department of a tertiary care center. PARTICIPANTS: Two hundred fifty-six CMT patients, from the ages of 9 days to 16yrs, with a mean follow-up period of 6.7 months. MAIN OUTCOME MEASURES: Correlation of the ultrasound appearance of the involved sternocleidomastoid (SCM) muscles with clinical features. The pathologic findings in diseased muscles from patients who underwent surgical intervention were also evaluated. RESULTS: Muscle abnormalities were identified ultrasonographically in 218 CMT patients (85%) and were classified into four types: a fibrotic mass in the involved muscle (type I, 15%); diffuse fibrosis mixing with normal muscle (type II, 77%) and without normal muscle in the involved muscle (type III, 5%); and a fibrotic cord in the involved muscle (type IV, 3%). Compared with type I patients, type IV patients were more likely to undergo surgical treatment (odds ratio = 31.54, p = .0196). Type III patients were more likely to undergo surgical treatment, although this tendency was not statistically significant. CONCLUSION: Ultrasonography can precisely identify pathologic changes in the involved SCM muscle of CMT patients. Type III and IV patients are more likely to require surgical intervention.

Adolescent↗

Three measures of mutagen sensitivity in a cancer-free population.

Different individuals appear to respond differently to the same carcinogen, and different mutagens act differently on cells. We conducted mutagen sensitivity assays by using three mutagens (bleomycin, a radiomimetic agent; 4-nitroquinoline-1-oxide [4-NQO], an ultraviolet light mimetic agent; and benzo[a]pyrene diol epoxide [BPDE], a tobacco mutagen) in parallel in healthy human subjects to determine the relationships among these assays. Our results showed that the mean breaks per cell values (b/c) (+/- SD) for bleomycin, 4-NQO, and BPDE sensitivity were 0.49 (+/- 0.26), 0.53 (+/- 0.30), and 0.66 (+/- 0.41), respectively. Age, sex, smoking status, and family history of cancer were not correlated with any of these mutagen sensitivities. Also, there was no correlation between bleomycin and 4-NQO or 4-NQO and BPDE sensitivity, but a weak correlation between bleomycin and BPDE was observed (correlation coefficient = 0.289; P = 0.001). When the 75th percentile of b/c was used as a cutoff point in each assay, only one individual (1.8%) was sensitive to all three mutagens. Ten individuals (17.9%) were sensitive to two mutagens, 20 (35.7%) to one mutagen, and 25 (44.6%) to none of three mutagens. Our study suggests that these three mutagens may involve different DNA damage and repair pathways. The lack of correlation between the assay results may indicate the necessity of using a battery of mutagen sensitivity tests to refine our ability to identify a subpopulation at high cancer risk.

4-Nitroquinoline-1-oxide↗

Noninvasive assessment of the viscoelasticity of peripheral arteries.

Currently used methods of examining the mechanical properties of blood vessel walls are either indirect or invasive, or measure vessel diameter and pressure waveforms at different sites. We developed a noninvasive technique to assess the mechanical properties and viscoelasticity of peripheral arteries. The pressure-strain elastic modulus (Ep) and the viscoelastic properties (energy dissipation ratio, EDR) of the common carotid artery (CCA), brachial artery (BA), radial artery (RA) and dorsalis pedis artery (DPA) were determined by means of palpating pressure and diameter distension waveforms extracted from high-resolution ultrasonography. The methodology was validated in vitro using an elastic tube phantom, as well as in vivo. In vivo study in 10 healthy volunteers (mean age 22 y) showed that the pressure-diameter curves were nonlinear, with an inflection at about 85-90 mmHg, and routed clockwise with slight hysteresis. The CCA (n = 5) had a mean diameter of 6.74 mm and the pulsatile diameter distension was 12.2%. The Ep calculated at the CCA was 0.44 x 10(6) dyne/cm2 with an EDR of 7.18%. The BA, RA and DPA (n = 10) had mean diameters of 3.91 mm, 2.21 mm and 2.12 mm; arterial strains of 4.60%, 4.25% and 8.91%; mean Ep of 1.39, 1.45, 0.90 x 10(6 )dyne/cm2; and mean EDRs of 6.34%, 6.15% and 5.60%, respectively. The method presented is relatively simple to implement clinically and has potential as a new diagnostic tool for detecting local vascular changes.

Adult↗

EMG power spectrum analysis of first dorsal interosseous muscle in pianists.

PURPOSE: Long-term piano training may induce potential biochemical and structural adaptations in hand intrinsic muscles or alter the motor strategy in the nervous systems. METHODS: This study investigated, by electromyography (EMG) and strain gauge, whether this pedagogical training is aerobic or anaerobic by nature. Changes in EMG power spectrum during incremental isometric muscle contractions before and after a sustained, fatiguing muscular performance were studied in the first dorsal interosseous muscle (FDI) of 13 female pianists and 15 sedentary controls. The maximal voluntary contraction (MVC) force of the FDI and the time needed to induce fatigue were also measured. RESULTS: During fatigue, the median frequency (MF) shifted toward the low frequencies in both groups. The MF of 50% and 25%MVC subsequent to fatigue were significantly lower than those before fatigue in the control group (104.0 +/- 45.5 Hz vs 116.7 +/- 41.4 Hz at 50%, P < 0.05; 114.7 +/- 43.4 Hz vs 123.3 +/- 46.7 Hz at 25%, P < 0.05). There were no significant MF changes within the pianists before and after fatigue. The root mean squares (RMS) of 50%, 25%, and 10%MVC of control subjects after fatigue were significantly higher than those before fatigue, but not in pianists. There was no difference in MF and RMS between the two groups at any level of %MVC before or after fatigue, but the pianists tended to show higher MF at each level of %MVC. Although the MVC was similar in both groups, the pianists, however, needed a much longer time to induce fatigue than controls (14.3 +/- 5.8 min vs 5.8 +/- 3.3 min, P < 0.005). CONCLUSIONS: These observations are discussed in terms of the training-induced metabolic adaptations, the changes in the strategy of motor unit recruitment, and the possibility of differences in muscle fiber composition. This study indicates that piano training should not be classified as power training, rather as endurance training. Such findings may also provide information about fine motor training for athletes and other professionals.

Adult↗

Presentation of autoantibody to proliferating cell nuclear antigen in patients with chronic hepatitis B and C virus infection.

OBJECTIVES: To study the association of antibodies to proliferating cell nuclear antigen (PCNA) in patients with chronic hepatitis B (HBV) and C (HCV) virus infection. METHODS: Sera from 243 patients with chronic HBV infection; 379 patients with chronic HCV infection; 80 patients with systemic lupus erythematosus (SLE); 28 patients with rheumatoid arthritis; 15 patients with Sjogren's syndrome; eight with polymyositis; eight with primary biliary cirrhosis; and 33 healthy control subjects were tested for the presentation of anti-PCNA antibodies by enzyme linked immunosorbent assay (ELISA) and immunoblotting using recombinant PCNA as antigen. The distribution of immunoglobulin isotypes of anti-PCNA antibody was measured by ELISA assay. RESULTS: By ELISA, anti-PCNA antibodies were detected in 30 (12.3%) patients with chronic HBV infection, 71 (18.7%) patients with chronic HCV infection, and five (6.3%) patients with SLE. The inhibition of binding with these sera by purified PCNA was shown to exceed 71%. By immunoblotting, the frequency of anti-PCNA in patients with chronic HBV and HCV infection was 17 of 243 (7%) and 41 of 379 (11%), respectively. Absorption studies on indirect immunofluorescence showed the typical nuclear speckled staining pattern by anti-PCNA sera was abolished by preincubation of sera with PCNA. Anti-PCNA antibody was not detected in sera from patients with autoimmune diseases except SLE. Anti-PCNA antibodies in patients with chronic HBV and HCV infection were predominantly IgG. CONCLUSION: These data suggest that anti-PCNA antibody are also present in patients with chronic HBV and HCV infection. Anti-PCNA antibody may not be specific for SLE.

Animals↗

The mechanical properties of the heel pad in unilateral plantar heel pain syndrome.

Plantar heel pain syndrome has been attributed to entrapment neuropathy, plantar fasciitis, calcaneal spurs, and stress fractures of the calcaneus. Although deteriorated mechanical properties of the heel pads may play an important role in the pathogenesis of heel pain syndrome, this has received little notice. In this study, a specially designed compression relaxation device with a push-pull scale and a 10-MHz linear array transducer was used to determine thickness of the heel pad under different loading conditions. Twenty consecutive patients aged 29 to 77 years with unilateral plantar heel pain syndrome were enrolled. Thickness of heel pad bilaterally was measured when the heel pad was compressed by serial increments of 0.5 kg to a maximum of 3 kg and then relaxed sequentially. The load-displacement curve during a loading-unloading cycle was plotted, and the compressibility index and energy dissipation ratio of the heel pad were calculated accordingly. Phase I displacement of the heel pad (from 0 to 1 kg load) on the painless side was greater than that on the painful side (P < 0.01), but there was no statistically significant difference between painless and painful sides in thickness of unloaded heel pads, compressibility index, or energy dissipation ratio (P > 0.05). In conclusion, the affected heel pad in plantar heel pain syndrome was stiffer under light pressure than the heel pad on the painless side. The changed nature of chambered adipose tissue in a painful heel pad may be responsible for its increased stiffness under light pressure.

Adipose Tissue↗

Mechanical properties of heel pads reconstructed with flaps.

We compared the mechanical properties of normal and reconstructed heel pads in seven patients. Four had latissimus dorsi flaps and one each an anterior thigh flap, a local dorsalis pedis flap and a sural arterial flap. The thickness of the heel pad was measured under serial incremental loads of 0.5 kg to a maximum of 3 kg and then relaxed sequentially. The load-displacement curve of the heel pad during a loading-unloading cycle was plotted and from this the unloaded heel-pad thickness (UHPT), compressibility index (CI), elastic modulus (Ep), and energy dissipation ratio (EDR) were calculated. The EDR was significantly increased in the reconstructed heels (53.7 +/- 18% v 23.4 +/- 6.5%, p = 0.003) indicating that in them more energy is dissipated as heat. Insufficient functional capacity in the reconstructed heel pad can lead to the development of shock-induced discomfort and ulceration.

Adult↗

Sonographic evaluation of the posterior cruciate ligament in amputated specimens and normal subjects.

The purpose of this study was to define the sonographic appearance and echogenicity of the normal posterior cruciate ligament. We examined the posterior cruciate ligament of five amputated specimens and five normal subjects using a 10 MHz linear array transducer. One K-wire was inserted into the substance of the posterior cruciate ligament of the amputated knee specimens to verify the location of the ligament on the sonogram. Various angles of insonation were used to examine the echogenicity of the posterior cruciate ligament. The results showed that the in situ posterior cruciate ligament appeared as a hypoechoic band relative to the surrounding tissue on sonograms, but it appeared hyperechoic when it was isolated and immersed in a water bath. The specific spatial orientation of the posterior cruciate ligament and anisotropy phenomenon contributed to the hypoechogenicity of the posterior cruciate ligament in situ on sonogram.

Adult↗

Sera from patients with scleroderma inhibit fibroblast micromotions monitored electrically.

OBJECTIVE: To investigate scleroderma fibroblast behavior, and the effect of different human sera on fibroblast behavior, we established a model using the newly developed electrical biosensor, electrical cell-substrate impedance sensing (ECIS). METHODS: Cellular locomotion, defined as cellular micromotion, measured by ECIS indicates the dynamic vertical motion of a given group of cells. The junctional resistance (Rb) between adjacent cells and the average height (h) between basal cell surface and substratum derived from ECIS were quantified for dermal fibroblasts obtained from patients with scleroderma and normal controls. The cellular micromotions of both scleroderma and normal control fibroblasts were compared in the presence of different human sera, including those from patients with scleroderma, systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) and from normal individuals. RESULTS: The Rb and h levels for scleroderma and normal fibroblasts were 2.7 omega.cm2, 150 nm and 0.8 omega.cm2, 303 nm respectively. The micromotions of scleroderma fibroblasts were more active than those of normal fibroblasts. Sera from patients with scleroderma can inhibit the micromotions of normal fibroblasts but not those of scleroderma fibroblasts, while sera from patients with SLE and SS have no inhibitory effect on either normal or scleroderma fibroblast micromotions. CONCLUSION: We have demonstrated the previously unrecognized characteristics of dermal fibroblasts and sera derived from patients with scleroderma. It is possible that in vivo activities cause scleroderma fibroblasts to display active cellular micromotions, while sera from patients with scleroderma inhibit the micromotions of normal fibroblasts. The use of ECIS technology has also provided a new approach to the study of scleroderma.

Aged↗

Marijuana use and increased risk of squamous cell carcinoma of the head and neck.

Marijuana is the most commonly used illegal drug in the United States. In some subcultures, it is widely perceived to be harmless. Although the carcinogenic properties of marijuana smoke are similar to those of tobacco, no epidemiological studies of the relationship between marijuana use and head and neck cancer have been published. The relationship between marijuana use and head and neck cancer was investigated by a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. Epidemiological data were collected by using a structured questionnaire, which included history of tobacco smoking, alcohol use, and marijuana use. The associations between marijuana use and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and passive smoking, the risk of squamous cell carcinoma of the head and neck was increased with marijuana use [odds ratio (OR) comparing ever with never users, 2.6; 95% confidence interval (CI), 1.1-6.6]. Dose-response relationships were observed for frequency of marijuana use/day (P for trend <0.05) and years of marijuana use (P for trend <0.05). These associations were stronger for subjects who were 55 years of age and younger (OR, 3.1; 95% CI, 1.0-9.7). Possible interaction effects of marijuana use were observed with cigarette smoking, mutagen sensitivity, and to a lesser extent, alcohol use. Our results suggest that marijuana use may increase the risk of head and neck cancer with a strong dose-response pattern. Our analysis indicated that marijuana use may interact with mutagen sensitivity and other risk factors to increase the risk of head and neck cancer. The results need to be interpreted with some caution in drawing causal inferences because of certain methodological limitations, especially with regard to interactions.

Adult↗

Chromosomal fragile sites and DNA amplification in drug-resistant cells.

It has been well established that DNA amplification is one of the important mechanisms by which cultured cells acquire resistance to many cytotoxic compounds. Amplification of important genes including those encoding oncoproteins, growth factors, their receptors and cell-cycle regulators has been reported in human neoplasms. Yet, despite intensive research since the first description of DNA amplification in cultured cells about 20 years ago, the mechanisms of DNA amplification remain largely unknown. Many models have been proposed to account for the diverse manifestations of amplified DNA in many different cell sources. It is not the intention of this commentary to review these many different models. Rather, we wil focus on the recent advances in this area of research, made mainly via the fluorescence in situ hybridization technique, that have revealed a fairly common chromosomal manifestation of amplified DNA in the drug-resistant hamster cell lines and have demonstrated the association of chromosomal fragile site breakage with early events in DNA amplification. These new developments underscore the importance of future research toward understanding the molecular bases of chromosomal fragile sites, including mechanisms involved in DNA strand breakage and repair, chromosomal translocations, and deletions, which may, in turn, provide important new insights into genomic plasticity and neoplastic transformation.

Animals↗