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Biomedical subjects

H C Chen

Publications and source records attributed to H C Chen.

At least 145 records · Page 8Linked to original sources

Postoperative radiotherapy for supratentorial malignant gliomas.

From January 1988 to December 1996, sixty-five patients with histologically confirmed supratentorial malignant gliomas were treated with postoperative radiation therapy in our department. They were subjected to this analysis according to different clinical and pathologic parameters. The overall 1-year, 2-year survival rate was 57% and 23%, respectively. With univariate analysis, age, postoperative Karnofsky performance status, duration of symptoms, multiplicity of lesions and the extent of surgery were identified as significant prognostic factors. With multivariate analysis, postoperative Karnofsky performance status and the extent of surgery continued to show independent prognostic significance on overall survival.

Combined Modality Therapy↗

Management of choroidal melanomas with linear accelerator-based stereotactic radiosurgery.

PURPOSE: To discuss the technical aspect, dose prescription, clinical results, and biological responsiveness of linear accelerator-based stereotactic radiosurgery for choroidal melanoma. METHODS: From March 1995 to December 1995, three choroidal melanoma patients were treated with Linac-based radiosurgery in our department. Two patients underwent one dose of radiosurgery with 18 and 20 Gy in single fraction, respectively. The third patient received two doses of radiosurgery with a total dose of 35 Gy. RESULTS: Follow-up time ranged from 19 to 25 months (median: 24 months). One patient had near-total regression, while the other two patients had partial response on the last MR images. Visual acuity was deteriorated in all patients. One patient developed a radiation-induced cataract in the treated eye. CONCLUSION: Linac-based radiosurgery is technically feasible for management of choroidal melanoma. Although visual acuity was not improved in these patients, they appreciated the preserving of the eyeball without affecting their general appearance.

Adult↗

Hypoxia/ischemia induces dephosphorylation of rat brain neuromodulin/GAP-43 in vivo.

The in vivo state of phosphorylation and the modification of two Cys residues of neuromodulin/ GAP-43 (Nm) were analyzed by electrospray ionization-mass spectrometry (ES-MS). The protein was purified from rat brain with homogenization buffer containing 1% Nonidet P-40, protease inhibitors, protein phosphatase inhibitors, and sulfhydryl reagent, 4-vinylpyridine. Nm was purified by HPLC and ion-exchange chromatography, and the various fractions were identified by ES-MS as unphosphorylated and mono-, di-, tri-, and tetraphosphorylated species. All of these Nm species contained 2 mol of added 4-vinylpyridine per mol of Nm, suggesting that the two Cys residues are in the reduced form in the brain. In vivo, the majority of Nm is in the phosphorylated form (approximately 80%), of which the levels of the mono- and diphospho forms are higher than those of the tri- and tetraphospho species. Four in vivo phosphorylation sites, Ser41, Thr95, Ser142, and Thr172, were identified by amino acid sequencing and tandem ES-MS of the peptides derived from Lys-C endoproteinase digestion. Among these sites, only Ser41 is a known target of PKC, whereas the kinases responsible for the phosphorylation of the other three novel sites are unknown. Hypoxia/ischemia caused a preferential dephosphorylation of Ser41 and Thr172, whereas Thr95 is the least susceptible to dephosphorylation.

Amino Acid Sequence↗

Modulation of dopamine transporter activity by nicotinic acetylcholine receptors and membrane depolarization in rat pheochromocytoma PC12 cells.

To elucidate the regulation of the rat dopamine transporter (rDAT), we established several PC12 variants overexpressing the rDAT. Treating these cells with a nicotinic agonist (1,1-dimethyl-4-phenylpiperazinium iodide, 30 microM) depolarized the plasma membrane potential from -31 +/- 2 to 43 +/- 5 mV and inhibited rDAT activity significantly in a calcium- and protein kinase C-independent manner. Membrane depolarization by a high external K+ concentration or two K+ channel blockers (tetraethylammonium hydroxide and BaCl2) also resulted in a marked inhibition of rDAT activity. Such inhibition of dopamine uptake is due to a reduction in Vmax, with no marked effect on the Km for dopamine. The potency of cocaine in inhibiting dopamine uptake was not significantly altered, whereas that of amphetamine was slightly enhanced by membrane depolarization. Removing extracellular Ca2+ or blocking the voltage-sensitive L-type calcium channels using nifedipine did not exert any significant effect on the inhibition of rDAT activity by depolarization. These data confirm that calcium influx on depolarization is not required for inhibition of the rDAT. Collectively, our data suggest that rDAT activity can be altered by a neurotransmitter that modulates the membrane potential, thus suggesting an exquisite mechanism for the fine-tuning of dopamine levels in the synapse.

Adrenal Gland Neoplasms↗

Induction of heat shock protein 70 protects mesangial cells against oxidative injury.

The heat shock response is an immediate cellular response to elevated temperatures and other types of injury that consists of the synthesis of so-called heat shock protein (hsp). This study was designed to investigate the production and the protective role of the 70 kDa hsp (hsp70) in cultured rat mesangial cells. When mesangial cells undergo thermal (45 degrees C, 15 min) stimulation, they express hsp70 mRNA expression and increased hsp70 protein production. Following this, Northern blots show an enhanced gene expression of hsp70 at one hour that reached a maximum by 12 hours after heat shock. The hsp70 protein production, estimated by Western blots, was detectable 12 hours after heat shock and reached a maximum by 36 hours. Oxidative injury generated by xanthine and xanthine oxidase inhibited cell survival and cellular proliferation, as measured by trypan blue exclusion and [3H]-labeled thymidine uptake. It did not affect hsp70 mRNA expression. Furthermore, when mesangial cells were preconditioned by heat shock, subsequent oxidative injury caused less inhibition of cell survival and cellular proliferation. Pretreatment of cells with quercetin, a transcription inhibitor, abolished the protective effect of heat shock on subsequent oxidative injury. We conclude that heat shock, not oxidative injury, induces hsp70 in mesangial cells, and this induction of hsp70 protects mesangial cells against subsequent oxidative injury.

Animals↗

Oromandibular reconstruction using a third free flap in sequence in recurrent carcinoma.

Successful results of a second microsurgical reconstructive attempt have been reported previously in recurrent oral carcinoma. However, the feasibility of a third free flap following a third excision has remained to be determined. Six oral carcinoma patients with multiple recurrences, surgical excisions and free flap reconstructions on three separate occasions are presented. Resections had a curative intent in all cases in the first and second ablations and in four of the six cases in the third one. Five radial forearm flaps and one double free flap were used for the first reconstruction. During the second reconstruction two radial forearm, two fibula osteoseptocutaneous, one double free flap and one rectus femoris flap were used to reconstruct the larger defects resulting from excision of the recurrent tumours. However, no vascularised bone transfers were performed following the third excision and soft tissue free flap plus plate option was used for segmental mandibular defects. There was one partial flap loss among 21 free flaps performed. Three patients died within an average of 8 months following the third reconstruction while the others remained alive, surviving an average of 6 months. In conclusion, a third free tissue transfer for reconstruction in multiply recurrent oral carcinoma was found to be feasible, safe and effective. The use of free flaps contributed to the prevention of complications in these difficult cases and enabled the patients to spend the remaining days of their lives outside hospital.

Adult↗

Site-directed mutagenesis of Asp313, Glu315, and Asp391 residues in chitinase of Aeromonas caviae.

Site-directed mutagenesis was used to explore the roles of amino acid residues involved in the activity of chitinase from Aeromonas caviae. Kinetic parameters for 4-methylumbelliferyl-N,N'-diacetyl-chitobiose or 4-methylumbelliferyl-N,N',N"-triacetylchitotriose hydrolysis were determined with wild-type and mutant chitinases. Chitinases with the mutations E315D (or Q) and D391E (or N) were severely impaired and had dramatically decreased kcat. However, the effect of the these mutations on the Km values were different. The function of the carboxyl group of Asp313 was partially replaced by the amide of Asn when the 4-methylumbelliferyl-N,N',N"-triacetylchitotriose substrate was used. Results indicated that Asp313, Glu315, and Asp391 might be the best candidates for the catalytic residues of chitinase A from Aeromonas caviae.

Aeromonas↗

Variant forms of DNA polymerase beta in primary lung carcinomas.

DNA polymerase beta (pol beta) provides most of the gap-filling synthesis at apurinic/apyrimidine sites of damaged DNA in the base excision repair pathway. A truncated form of the pol beta protein is expressed in colon and breast cancers. However, the role of the pol beta gene in lung cancer is not known. Thus, we investigated a possible occurrence of pol beta variants in primary lung tumors. The entire cDNA of pol beta obtained by RT-PCR amplification was analyzed for nucleotide sequencing in lung tumor and matched normal lung tissue of the same patient. Three types of variants were detected in squamous, non-small, or large cell carcinomas. The most common variant was a deletion of 87 bp from pol beta cDNA at a site corresponding to exon 11. In addition, a variant exhibiting deletions of 87 and 140 bp together with an insertion of 105 bp was identified in three lung tumors. This is the first report of the occurrence of pol beta variants, possibly splicing variants, in lung cancer. A truncated pol beta protein resulting from variant forms of the gene may impact the function of the enzyme and increase susceptibility to carcinogenesis.

Aged↗

Combined ischemic preconditioning and laser Doppler measurement for early division of pedicled groin flap.

OBJECTIVES: The main disadvantage of the pedicled groin flap for hand reconstruction is the long period of immobilization required. Early division of the pedicled groin flap is desirable for both patients and surgeons. The aims of this study were to investigate whether ischemic preconditioning can effectively accelerate the neovascularization of the junction between the donor and recipient sites in the pedicled flap, and the most objective method of judging the timing of early division of the pedicled groin flap. This report is the first prospective study to use ischemic preconditioning for early division of pedicled cutaneous flap combined with laser Doppler measurement. METHODS: The severe hand injuries of 12 patients were reconstructed by using the pedicled groin flap method. The ischemic preconditioning program was prospectively performed as scheduled for 5 to 7 days postoperatively. The pedicled groin flap was monitored with laser Doppler when the flap was elevated, inset, with clamping and nonclamping postoperatively. RESULTS: Eleven of the 12 pedicled groin flaps were divided safely and survived completely. Only one pedicled groin flap with a simultaneous harvest of iliac bone graft had partial flap loss, giving a success rate of 90.1%. CONCLUSION: With ischemic preconditioning, the pedicled groin flap can be safely divided postoperatively at a mean period of 8.4 days according to the laser Doppler measurement, especially when the perfusion unit ratio of clamping over nonclamping reaches more than 36.6%.

Adult↗

Microsurgical combined scapular/parascapular flap for reconstruction of severe neck contracture: case report and literature review.

OBJECTIVE: The reconstruction for severe neck contracture is difficult, because it may include not only the necessity the use of a large flap but also the ability for three-dimensional movement of the neck. METHODS: A 41-year-old woman sustained a severe neck contracture with retraction of the lower lip and limited range of neck motion after a chemical burn. We used the combined scapular/parascapular flap to reconstruct the soft-tissue defect in the neck after excision of hypertrophic scar and release of contracture. The scapular portion was transferred to cover the defect vertically, and the parascapular portion was transferred to cover the transverse portion of the neck. This kind of design would allow the patient to move her neck more easily. RESULTS: Postoperatively, the range of motion of the neck was full in the vertical and horizontal directions after 6 months of rehabilitation. Also, the patient was satisfied with the final aesthetic results. CONCLUSION: The microsurgical combined scapular/parascapular flap, providing a large area of tissue for coverage in three dimensions with a reliable blood supply by only one pedicle anastomosis during surgery, is a good option for reconstruction of the severe neck contracture. We classify the inset of the combined scapular/parascapular flap into three types with six subtypes, according to the location of defects and the relation of the parascapular flap to the scapular flap.

Adult↗

Systematic management of osteoradionecrosis in the head and neck.

OBJECTIVES: Osteoradionecrosis is one of the most serious and devastating complications of radiotherapy. The proper management of osteoradionecrosis is currently undetermined. The objective of this study is to evaluate the treatment results of a systematic approach to osteoradionecrosis. STUDY DESIGN: A prospective study of a systematic approach to osteoradionecrosis in the head and neck area was undertaken. METHODS: From July 1993 to June 1998, 33 cases of osteoradionecrosis in the head and neck area were treated using a systematic approach that combined sequestrectomy and hyperbaric oxygen therapy. RESULTS: Seven (21%) had recurrent cancer. The control rate of the other 26 osteoradionecrosis cases was 77% (20/26). CONCLUSIONS: Persistent osteoradionecrosis, despite diligent radical treatment, raises the suspicion of recurrent cancer. Extensive osteoradionecrosis with a multiple discharging fistula, a large area of exposed necrotic bone, or a coexistent fracture should be treated primarily with radical sequestrectomy and microvascular free flap reconstruction. Surgery still plays a major role in controlling osteoradionecrosis, and hyperbaric oxygen therapy is adjuvant.

Bone Diseases↗

Double free flaps in reconstruction of extensive composite mandibular defects in head and neck cancer.

Extensive composite defects of the lower jaw are defined as those that involve skin, mandible, oral mucosa, and soft tissues. The enormous size and multilayered nature of these defects challenge most of the current reconstructive techniques. For reconstruction of extensive composite mandibular defects in 36 advanced oral cancer patients, two free flaps were used simultaneously in a complementary fashion. The aim was to provide bone reconstruction and adequate soft-tissue coverage in an optimal form. Primary reconstruction was carried out in 34 of 36 cases. The fibula osteoseptocutaneous-radial forearm fasciocutaneous flap combination was most commonly used (n = 20), followed by the fibula osteoseptocutaneous-rectus abdominis myocutaneous flap (n = 11). The other combinations included the fibula osteoseptocutaneous-tensor fasciae latae, the fibula osteoseptocutaneous-rectus femoris, the iliac crest-radial forearm, and the iliac crest-tensor fasciae latae flaps. In 11 cases, the second free flaps were attached to the distal runoff of the first free flaps because of unavailability of recipient vessels. The mean operation time was 12 hours 10 minutes. The complete flap survival rate was 93 percent (67 of 72 flaps) with 2.8 percent total (2 of 72) and 4.2 percent partial (3 of 72) flap failures. Median follow-up time was 14 months, and 44 percent of the patients were alive at the time of evaluation, surviving an average of 36 months. The average survival time for those who died was 11.1 months. The authors believe that in selected cases the double free-flap procedure for one-stage reconstruction of massive mandibular defects is justified because it is safe and effective and improves the quality of life and the number of days spent outside of the hospital for these patients.

Adult↗

Microsurgical reconstruction in recurrent oral cancer: use of a second free flap in the same patient.

Primary microsurgical reconstruction is the treatment of choice for ablative defects of oral carcinoma. As a result of this trend, more and more patients with recurrent oral carcinoma who have been initially treated with surgical excision and reconstructed with free flaps are being seen. However, a second microsurgical reconstruction attempt in these cases raises questions about the flap choices, availability of recipient vessels, and effects of previous treatment modalities. Herein, 35 patients with perioral carcinoma who had two successive tumor resections and reconstruction with free flaps on each occasion are presented. A total of 75 free tissue transfers were carried out for the first and second reconstructions. After the first tumor resection, 28 radial forearm fasciocutaneous flaps, 7 fibula osteoseptocutaneous flaps, 1 iliac osteomyocutaneous flap, and 2 rectus abdominis myocutaneous flaps were used. For reconstruction after the recurrence, 17 radial forearm fasciocutaneous flaps, 13 fibula osteoseptocutaneous flaps, 3 rectus abdominis myocutaneous flaps, 2 anterolateral thigh flaps, 1 jejunum flap, and 1 tensor fasciae latae flap were used. More vascularized bone transfers were performed during the second reconstruction since the excision for the recurrence frequently required segmental mandibulectomy. The complete flap survival rate was 97.3 percent and 94.6 percent with a reexploration rate of 7.9 percent and 13.5 percent for the first and second free tissue transfers, respectively. The mean follow-up time throughout the procedures was 37.5 months. Disease-free interval between reconstructions was 20.8 months. At the time of evaluation, 54.3 percent of the patients were surviving an average of 19 months since the second reconstruction. The results suggest that free flaps represent an important option in reconstruction of recurrent perioral carcinoma cases undergoing reexcision. When used in this indication they are as safe and effective as the initial procedure.

Adult↗

Free fibula osteoseptocutaneous-pedicled pectoralis major myocutaneous flap combination in reconstruction of extensive composite mandibular defects.

Lateral composite mandibular defects resulting from excision of advanced oral carcinoma often require mandible, intra-oral lining, external face, and soft-tissue bulk reconstruction. Ignorance of importance soft-tissue deficit in those patients may cause significant morbidity and functional loss. Such defects, therefore, can be reconstructed best with a double free flap technique. However, this procedure may not be feasible for every patient or surgeon. An alternative procedure is a free fibula osteoseptocutaneous flap combined with a pedicled pectoralis major myocutaneous flap. This combination was used in reconstruction of extensive composite mandibular defects in 14 patients with T3/T4 oral squamous cell carcinoma. All patients were men, and the average age was 54.3 years. The septocutaneous paddle of the fibula flap was used for the mucosal lining of the defects while the bony part established the rigid mandibular continuity. The pectoralis major flap then covered the external skin defect in the face and cheek, and the dead spaces left by the extirpated masticator muscles, buccal fat, and parotid gland. One free fibula flap failed totally, and one pectoralis major flap developed marginal necrosis. At the time of final evaluation, nine patients (64.3 percent) were alive, surviving an average of 25.7 months. All patients eventually regained their oral continence and an acceptable cosmetic appearance. In conclusion, the fibula osteoseptocutaneous flap plus regional myocutaneous flap choice is a successful and technically less demanding alternative to the double free flap procedures in reconstruction of extensive lateral mandibular defects.

Adult↗

Management of secondary soft-tissue deficits following microsurgical head and neck reconstruction by means of another free flap.

Secondary soft-tissue deficits may develop following a microsurgical reconstruction in the head and neck region because of inadequate planning or chronic effects of radiotherapy. Although most cases could be managed with alternative methods, free flaps might be necessary in difficult cases. Herein are described 11 cases of microsurgical head and neck reconstruction in which secondary soft-tissue deficits required transfer of another soft-tissue free flap. All patients had malignant tumors treated with surgical resection, and their defects were reconstructed with free flaps. Seven patients received either preoperative or postoperative adjunctive radiotherapy. These patients gradually developed signs and symptoms of soft-tissue deficiency in the reconstructed area, and a soft-tissue free flap transfer was required for treatment within an average of 21.5 months of their initial reconstruction. Five rectus abdominis, one rectus femoris, one latissimus dorsi, one tensor fasciae latae myocutaneous, one radial forearm, one medial arm, and one dorsalis pedis flap were used for this purpose. All flaps survived completely. The average follow-up time was 32 months. Significant improvement was achieved in all cases, and no further major surgical procedures were required. Secondary soft-tissue deficits that could not be predicted or prevented during the initial microsurgical reconstruction may be treated successfully by a subsequent free soft-tissue transfer in selected cases.

Adult↗