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Biomedical subjects

A D Chan

Publications and source records attributed to A D Chan.

12 recordsLinked to original sources

Detection of occult metastatic breast cancer cells in blood by a multimolecular marker assay: correlation with clinical stage of disease.

Currently, molecular markers offer the unique opportunity to identify occult metastasis in early stage cancer patients not otherwise detected with conventional staging techniques. To date, well-characterized molecular tumor markers to detect occult breast cancer cells in blood are limited. Because breast tumors are heterogeneous in tumor marker expression, we developed a "multimarker" reverse transcription-PCR assay combined with the highly sensitive electrochemiluminescence automated detection system. Breast cancer cell lines (n = 7), primary breast tumors (n = 25), and blood from normal donors (n = 40) and breast cancer patients [n = 65; American Joint Committee on Cancer (AJCC) stages I-IV] were assessed for four mRNA tumor markers: beta-human chorionic gonadotropin (beta-hCG), oncogene receptor (c-Met), beta 1-->4-N-acetylgalactosaminyl-transferase, and a tumor-associated antigen (MAGE-A3). None of the tumor markers were expressed in any normal donor bloods. Breast cancer cell lines and primary breast tumors expressed beta-hCG, c-Met, beta 1-->4-N-acetylgalactosaminyl-transferase, and MAGE-A3 mRNA. Of the 65 breast cancer patient blood samples assessed, 2, 3, 15, 49, and 31% expressed 4, 3, 2, 1, and 0 of the mRNA tumor markers, respectively. At least two markers were expressed in 20% of the blood specimens. The addition of a combination of markers enhanced detection of systemic metastasis by 32%. In patient blood samples, the MAGE-A3 marker correlated significantly with tumor size (P = 0.0004) and AJCC stage (P = 0.007). The combination of beta-hCG and MAGE-A3 mRNA markers correlated significantly with tumor size (P = 0.04), and the marker combination c-Met and MAGE-A3 showed a significant correlation with tumor size (P = 0.005) as well as AJCC stage (P = 0.018). A multimarker reverse transcription-PCR assay that correlates with known clinicopathological prognostic parameters may have potential clinical utility by monitoring tumor progression with a blood test.

Adult↗

Myo-electric signals to augment speech recognition.

It is proposed that myo-electric signals can be used to augment conventional speech-recognition systems to improve their performance under acoustically noisy conditions (e.g. in an aircraft cockpit). A preliminary study is performed to ascertain the presence of speech information within myo-electric signals from facial muscles. Five surface myo-electric signals are recorded during speech, using Ag-AgCl button electrodes embedded in a pilot oxygen mask. An acoustic channel is also recorded to enable segmentation of the recorded myo-electric signal. These segments are processed off-line, using a wavelet transform feature set, and classified with linear discriminant analysis. Two experiments are performed, using a ten-word vocabulary consisting of the numbers 'zero' to 'nine'. Five subjects are tested in the first experiment, where the vocabulary is not randomised. Subjects repeat each word continuously for 1 min; classification errors range from 0.0% to 6.1%. Two of the subjects perform the second experiment, saying words from the vocabulary randomly; classification errors are 2.7% and 10.4%. The results demonstrate that there is excellent potential for using surface myo-electric signals to enhance the performance of a conventional speech-recognition system.

Adult↗

Sentinel node detection in malignant melanoma.

The initial application of intraoperative lymphatic mapping and sentinel lymphadenectomy followed by selective complete lymphadenectomy (LM/SL/SCLND) was in melanoma. This arose as a solution to the ongoing debate concerning immediate vs. delayed lymph node dissection. Acceptance of the concept and advances in nuclear medicine, surgery, and pathology aspects of the sentinel node procedure have brought it into widespread use for melanoma and have expanded its application for other solid tumors that progress through the lymphatic route. Although the diagnostic accuracy of the procedure has been demonstrated in multicenter trials, caution should be exercised regarding therapeutic aspects until definitive benefit can be shown from well-designed clinical trials. Current issues of active discussion and debate are reviewed including ideal nomenclature, clinical significance of occult metastatic disease, quality assurance, and the role of LM/SL/SCLND outside high-volume melanoma centers.

Animals↗

The concept of sentinel node localization: how it started.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) followed by selective complete lymphadenectomy (SCLND) has revolutionized the management of the regional lymph node basin in patients with solid tumors. Many investigators over the centuries have contributed to the understanding of the progression of tumor cells through the lymphatic system. This article discusses the conceptual background for the development of LM/SL in the original model of melanoma. The sentinel node hypothesis has been validated by a multicenter clinical trial showing that LM/SL in melanoma can be accurately performed in a uniform manner by multidisciplinary teams at cancer centers worldwide. Although the diagnostic and prognostic accuracy of LM/SL has been established, demonstration of the therapeutic use of this procedure awaits analysis of survival data from the multicenter randomized trial of wide excision alone versus wide excision plus LM/SL/SCLND.

Humans↗

Judging the therapeutic value of lymph node dissections for melanoma.

BACKGROUND: The management of the regional lymph nodes remains controversial for early-stage melanoma and for those patients with lymph node metastases; American Joint Committee on Cancer stage III. This study examines the importance of quality of the surgical resection measured by the extent of lymph node dissection (quartile of the total number of lymph nodes removed) to determine if this factor is an important prognostic factor for survival. STUDY DESIGN: We reviewed our computer-assisted database of more than 8,700 melanoma patients prospectively collected from 1971 through the present to identify patients who underwent lymph node dissection for stage III melanoma. We included only patients who had their nodal dissections performed at our institute. Patients who underwent sentinel lymph node dissection were excluded. These patients were then analyzed as a group and by individual lymphatic basins: cervical, axillary, and inguinal basins. Univariate and multivariate analyses were used to examine the model that included tumor burden, thickness of the primary melanoma, gender, age, clinical status of the lymph nodes (palpable versus not palpable), and the primary site. The survival and recurrence rates were analyzed using the Cox proportional hazards model. RESULTS: Five hundred forty-eight patients underwent regional lymph node dissections. Of these patients, 214 underwent axillary dissections, 181 inguinal dissections, and 153 cervical dissections. The extent of the nodal dissections was based on the quartile of nodes excised, ranging from 1 to 98 (mean +/- SD = 25.8 +/- 15.8). Patients were stratified by tumor burden and quartile of number of lymph nodes removed. The overall 5-year survival of patients with four or more lymph nodes having tumor and the highest quartile of lymph nodes removed was 44% and was 23% for the lowest quartile of total lymph nodes excised (p = 0.05). By univariate analysis, tumor burden (p = 0.0001), quartile of total lymph nodes removed (p = 0.043), and primary site (p = 0.047) were statistically significant for predicting overall survival. Gender, clinical status of the nodes, primary tumor thickness, age, and dissected basin were not significant (p > 0.05). By multivariate analysis only the tumor burden (p = 0.0001) and quartile of lymph nodes resected (p = 0.044) were statistically significant. CONCLUSIONS: The extent of lymph node dissection for melanoma when analyzed by quartiles is an independent factor in overall survival. This factor appears to be more important with increasing tumor burden in the lymphatic basin. The extent of lymph node dissection should be considered as a prognostic factor in the design of clinical trials that involve stage III melanoma.

Female↗

Imaging of subcapsular hepatic and renal hematomas in pregnancy complicated by preeclampsia and the HELLP syndrome.

The purpose of this report is to provide an illustrative case of spontaneous hepatic and renal hematomas that occurred during a pregnancy complicated by preeclampsia and the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. The sonographic and computed tomographic findings included intrahepatic, subcapsular hepatic, and extracapsular perihepatic hematomas in addition to a large subcapsular renal hematoma. Since hepatic and renal hematomas that occur in association with preeclampsia and the HELLP syndrome are rare but potentially life-threatening complications, prompt laboratory and radiologic evaluations are essential and may reduce the associated morbidity and mortality.

Adult↗

Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy.

High resolution 1H nuclear magnetic resonance spectroscopy has been used to investigate and compare the metabolic profiles of normal and osteoarthritic synovial fluids in a canine model of osteoarthritis. The spectra of osteoarthritic synovial fluid showed (a) increased concentrations of lactate, pyruvate, lipoprotein-associated fatty acids, and glycerol as well as the ketones hydroxybutyrate and hydroxyisobutyrate, (b) reduced levels of glucose, and (c) elevated levels of N-acetylglycoproteins, acetate, and acetamide compared with healthy normal canine synovial fluid. An increase was also observed in the concentrations of the amino acids alanine and isoleucine. These results suggest that (a) the intraarticular environment in canine osteoarthritis is more hypoxic and acidotic than in a normal joint, (b) lipolysis may play an increasingly important role as a source of energy in osteoarthritis, and (c) the N-acetylglycoprotein polymer component of synovial fluid (mostly hyaluronan) seems to be increasingly fragmented and degraded into acetate by way of an acetamide intermediate with progressive osteoarthritis. The observed changes in the biochemical profile of canine osteoarthritic synovial fluid may be useful in understanding alterations in joint metabolism consequent to arthritic diseases and helpful in identifying potential markers of osteoarthritis.

Animals↗

Errors associated with the use of adaptive differential pulse code modulation in the compression of isometric and dynamic myo-electric signals.

Muscle activity produces an electrical signal termed the myo-electric signal (MES). The MES is a useful clinical tool, used in diagnostics and rehabilitation. This signal is typically stored in 2 bytes as 12-bit data, sampled at 3 kHz, resulting in a 6 kbyte s-1 storage requirement. Processing MES data requires large bit manipulations and heavy memory storage requirements. Adaptive differential pulse code modulation (ADPCM) is a popular and successful compression technique for speech. Its application to MES would reduce 12-bit data to a 4-bit representation, providing a 3:1 compression. As, in most practical applications, memory is organised in bytes, the realisable compression is 4:1, as pairs of data can be stored in a single byte. The performance of the ADPCM compression technique, using a real-time system at 1 kHz, 2 kHz and 4 kHz sampling rates, is evaluated. The data used include MES from both isometric and dynamic contractions. The percent residual difference (PRD) between an unprocessed and processed MES is used as a performance measure. Errors in computed parameters, such as median frequency and variance, which are used in clinical diagnostics, and waveform features employed in prosthetic control are also used to evaluate the system. The results of the study demonstrate that the ADPCM compression technique is an excellent solution for relieving the data storage requirements of MES both in isometric and dynamic situations.

Electromyography↗

Active immunotherapy with allogeneic tumor cell vaccines: present status.

This review will concentrate on allogeneic vaccines for melanoma The important principles of melanoma vaccine effectiveness are discussed in detail, followed by a review of the progress of several clinical trials investigating allogeneic vaccines. No therapeutic cancer vaccine has yet been approved for general use by the US Food and Drug Administration. However, much progress has been made in the field of vaccine immunotherapy, especially for the treatment of melanoma. Active immunotherapy with tumor vaccines is progressing rapidly as an emerging option for cancer therapy.

Antigens, Neoplasm↗

Arthroscopic anterior cruciate ligament transection induces canine osteoarthritis.

OBJECTIVE: To determine whether arthroscopic anterior cruciate ligament (ACL) transection in the canine knee can be an effective alternative method for creating canine osteoarthritis (OA). METHODS: Six adult dogs underwent arthroscopic examination of the left knee with a 2.7 mm 30 degrees fiberoptic arthroscope. The articular surfaces of the femoral condyles, tibial plateaus, and patella were examined for evidence of OA. The ACL was directly visualized and transected. Care was taken to avoid iatrogenic articular cartilage injury. The animals were sacrificed 2 to 6 months after ACL transection. Both the ACL transected and ACL intact knees from each animal were assessed for gross pathology and histology. RESULTS: The dogs experienced minimal perioperative pain and rapidly returned to their preinjury level of activity. Gross and histological examination of articular cartilage confirmed this approach induced OA in every ACL transected knee. No contralateral ACL intact knee developed degenerative OA changes. CONCLUSION: Arthroscopic ACL transection is an effective method for creating canine OA. This approach has several methodological advantages relative to other techniques.

Animals↗

Bilateral canine model of osteoarthritis.

OBJECTIVE: To determine whether bilateral arthroscopic anterior cruciate ligament (ACL) transection creates symmetrical osteoarthritis (OA) in canine knees. METHODS: Six dogs underwent bilateral arthroscopic ACL transections. The animals were sacrificed at intervals ranging from 2 to 12 months post ACL transection. Both knees in each animal were assessed for gross pathology, histology, and biochemistry. RESULTS: The limited invasiveness of arthroscopic ACL transection allowed bilateral ACL transections to be performed with minimal animal morbidity. Gross pathological, histological, and biochemical assessments of bilaterally ACL transected canine knees consistently confirmed the induction of OA changes in both knees. Of note, there was no significant difference in the degree of articular cartilage degeneration created in each pair of knees. CONCLUSION: Bilateral ACL transection induces symmetrical canine knee OA. This approach provides a potent model for investigating fundamental OA mechanisms and therapeutic approaches, since one knee can be experimentally manipulated while the other knee is used as a control. This allows each animal to be its own internal control, avoiding the interanimal variability associated with the unilateral canine OA model.

Animals↗