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Biomedical subjects

J S Sham

Publications and source records attributed to J S Sham.

At least 73 records · Page 4Linked to original sources

Evaluation of cervical nodal necrosis in nasopharyngeal carcinoma by computed tomography: incidence and prognostic significance.

PURPOSE: The purpose was to study the prognostic value of contrast-enhanced computed tomography (CT) nodal necrosis in nasopharyngeal carcinoma. PATIENTS AND METHODS: One hundred sixty-one patients with newly diagnosed nasopharyngeal carcinoma and nodal metastases were reviewed. Forty patients also received cisplatin-based neoadjuvant chemotherapy in addition to radiotherapy. Nodal necrosis was defined as presence of hypodense areas in more than 33% of the node. Nodal response rate to chemotherapy, overall nodal control rate, local control rate, distant failure rate, overall relapse-free survival rate, and overall and cause-specific survival rates were compared between patients with and without nodal necrosis. Multivariate analysis was also performed. RESULTS: The incidence of nodal necrosis was 22.9%. Overall nodal response rates to chemotherapy were 88.9% (8/9) in patients with nodal necrosis and 74.2% (23/31) in those without. No significant differences in nodal control rate, local control rate, distant failure rate, and overall and cause-specific survival rates were found. Five-year overall relapse-free survival rate was lower in patients with cervical nodal necrosis (36%) as compared with those without (53%, p = .04). Multivariate analysis, however, did not confirm cervical nodal necrosis to be an independent prognostic factor. CONCLUSIONS: Presence of nodal necrosis in nasopharyngeal carcinoma does not affect nodal response to chemotherapy and nodal control by radiotherapy with or without chemotherapy. Cervical nodal necrosis does not appear to be an independent factor in predicting treatment outcome. Further studies to correlate nodal density with oxygenation status as well as tumor cell kinetics are warranted.

Adult↗

Acetylcholine increases intracellular calcium of arterial chemoreceptor cells of adult cats.

Acetylcholine increases intracellular calcium of arterial chemoreceptor cells of adult cats. J. Neurophysiol. 78: 2388-2395, 1997. Several neurotransmitters have been reported to play important roles in the chemoreception of the carotid body. Among them acetylcholine (ACh) appears to be involved in excitatory processes in the cat carotid body. As one of the steps to elucidate possible roles of ACh in carotid body chemoreception in the cat, we examined the effect of ACh on intracellular calcium concentration ([Ca2+]i) of cultured carotid body cells. The carotid body from adult cats was dissociated and cultured for up to 2 wk. [Ca2+]i was measured from clusters of cells with a microfluorometric technique using Indo-1 AM. Experiments were performed at 37 degrees C, and cells were continuously superfused with modified Krebs solutions equilibrated with 5% CO2-16% O2-79% N2. ACh (100 mu M) caused a marked increase in [Ca2+]i in approximately 70% of clusters, and the responses to 1-300 mu M of ACh were concentration dependent. The magnitude and kinetics of the ACh response were mimicked by the application of nicotine, whereas muscarinic agonists, pilocarpine, and muscarine failed to evoke a similar response. ACh-induced increase in [Ca2+]i was dependent on extracellular Ca2+: it was greatly reduced or completely abolished by a transient removal of extracellular Ca2+. The response was consistently but only partially reduced by caffeine (5 mM) or nifedipine (10 mu M). The effect of mecamylamine (100 mu M) was inhibitory but small. Moreover, the increase in [Ca2+]i in response to ACh was also observed in some clusters that did not respond to high K (100 mM) Krebs. These results suggest that ACh increases [Ca2+]i of cultured carotid body cells by activating neuronal nicotinic ACh receptors, leading to Ca2+ influx via nicotinic channels. In addition, other pathways such as Ca2+ influx through L-type calcium channels, perhaps secondary to membrane depolarization, and Ca2+ release from intracellular stores may participate in increasing [Ca2+]i in response to ACh. Muscarinic receptors appear to play only a small role, if any.

Acetylcholine↗

Tachykinin-independent effects of capsaicin on smooth muscle in human isolated bronchi.

Contractile and relaxant responses to capsaicin and resiniferatoxin were examined in human isolated bronchus (5-12 mm o.d.). Bronchi isolated from 10 of 16 lungs contracted in response to capsaicin. The contractions averaged 20% of maximal contraction at 1 microM and averaged > 40% maximal contraction at 300 microM (the highest concentration studied). The capsaicin-induced contractions were mimicked by resiniferatoxin (0.1-10 microM) and inhibited by the putative capsaicin receptor antagonist, capsazepine (10 microM). The contractile response to capsaicin was not affected by the potent NK-2 selective antagonist SR 48968 (0.3 microM), whereas responses to concentrations of neurokinin A (10 nM), neurokinin B (0.1 microM), substance P (1 microM), neuropeptide gamma (10 nM), and neuropeptide K (10 nM) which produced similar-size contractions were almost abolished by 0.1 microM SR 48968. The bronchi isolated from 8 of 16 lungs also exhibited relaxations in response to capsaicin. Capsaicin-induced relaxations were not inhibited by the nitric oxide synthase inhibitor L-nitro-n-arginine (10 microM). In whole-cell patch-clamp experiments on human cultured airway smooth muscle cells, capsaicin was found to enhance outward currents due to the activation of charybdotoxin-sensitive large conductance Ca2+-activated K+ channels. Neither the capsaicin-induced contractions nor the relaxations were mimicked by angiotensin II, bombesin, or calcitonin gene-related peptide at concentrations up to 1 microM. These results suggest that capsaicin and resiniferatoxin can alter smooth muscle tone, but this response does not appear to involve substance P or related neurokinins. Relaxations to capsaicin may, however, involve the activation of large conductance Ca2+-activated K+ channels.

Adult↗

Imaging of maxillary osteoradionecrosis.

Over a 3-year period, four cases of maxillary osteoradionecrosis were diagnosed in patients undergoing radiotherapy for nasopharyngeal carcinoma at the Queen Mary Hospital, Hong Kong, giving an estimated incidence of 0.8%. Patients with this complication presented after a mean period of 34 months post-radiotherapy. Risk factors that were identified were dental problems, and more than one full course of radical radiotherapy. Serial CT scans in the axial and coronal planes were useful in demonstrating the development, extent and features of maxillary osteoradionecrosis such as bony sclerosis, the destruction of maxillary antral walls and adjacent bony structures, and in excluding recurrent tumour.

Adult↗

Nasopharyngeal carcinoma research in Hong Kong in the past decade.

OBJECTIVE: To review the research carried out in Hong Kong on nasopharyngeal carcinoma (NPC) over the past 10 years. METHODS: The literature published in Hong Kong over the past 10 years on nasopharyngeal carcinoma were reviewed in the light of other important international publications on the same subject. RESULTS: The research carried out in Hong Kong covers etiology, natural behavior, treatment and prognosis of NPC. These studies not only elucidated the different aspects of NPC, many of these new findings will also guide future directions of research. CONCLUSIONS: Major efforts have been made to research into the various aspects of NPC with important findings which will translate into better treatment results. As this tumor is uncommon in other parts of the world, continued efforts to improve the prevention, early diagnosis, treatment and care of this tumor are required in China.

Carcinoma in Situ↗

Sensorineural hearing loss in patients treated for nasopharyngeal carcinoma: a prospective study of the effect of radiation and cisplatin treatment.

PURPOSE: The pattern of sensorineural hearing loss (SNHL) after primary treatment for nasopharyngeal carcinoma (NPC) was studied, and the effect of cisplatin, radiotherapy does, and fractionation were evaluated. METHODS AND MATERIALS: One hundred thirty-two patients, 227 ears, and 1100 audiogram reports were analyzed. Radiotherapy dose ranged from 59.5 to 76.5 Gy. Fifty-two patients received preirradiation cisplatin, total dose 100-185 mg/m(2). Serial postirradiation bone conduction thresholds at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz were compared with pretreatment thresholds at respective frequencies. Increase of at least 15 dB was considered as significant and was further grouped as transient or persistent SNHL. Univariate and multivariate analyses were performed to identify predicting factors for persistent SNHL. RESULTS: At median follow-up of 30 months, 24.2% of ears developed persistent SNHL. High frequency was more affected than low frequencies, 22 vs. 5.3%. Males were more affected than females, 29.4 vs. 15.5%, p = 0.0132. Incidence of persistent SNHL increased with age, with 0, 17.2, and 37.4% of patients aged under 30, between 30-50 and over 50 affected, respectively, p = 0.0001. High incidence was found in patient with postirradiation serous otitis media (SOM), 46.9%. Chemotherapy with cisplatin and radiation dose or fractionation had no significant effect. Multivariate analysis confirmed age, sex, and postirradiation SOM as significant prognostic factors for persistent SNHL. CONCLUSIONS: Transient and persistent SNHL occurred after radiotherapy, more commonly affecting high frequency. A low dose of preirradiation cisplatin did not increase the risk. A dose fractionation effect of radiotherapy was not confirmed in this study.

Adolescent↗

Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma. A significant factor in local control and distant metastasis.

BACKGROUND: This study was conducted to evaluate the prognostic value of paranasopharyngeal extension in local control and distant metastasis in patients with nasopharyngeal carcinoma. METHODS: Three hundred and sixty-four patients with newly diagnosed nasopharyngeal carcinoma without distant metastasis were reviewed. Patients were staged according to Ho's staging system. Using a semiquantitative method, tumor extension into the paranasopharyngeal space was graded as: 0: no extension; 1: extension to the retrostyloid space; 2: extension to the prestyloid space; and 3: extension to the anterior part of the masticator space. All patients received radiotherapy as primary treatment. Median follow-up time was 45 months (range, 4.7 to 76.5 months). Relapse free, local relapse free, and distant metastasis free survival were estimated using the Kaplan-Meier method. Cox regression was also performed to adjust for prognostic factors. RESULTS: The incidence of paranasopharyngeal extension was high (72.5%). Of these patients, 65.5% had Grade 2 or 3 extension. The 5-year relapse free survival rates for Grade 0, 1, 2, and 3 extension were 76%, 70%, 46%, and 43%, respectively. The main difference was between Grade 0/1 and Grade 2/3 extension, the latter having a lower 5-year local control rate (86% in Grade 0/1 vs. 72% in Grade 2/3; P < 0.0001) and distant metastasis free survival rate (87% in Grade 0/1 vs. 68% in Grade 2/3; P = 0.0002). Multivariate analysis showed that Grade 2/3 paranasopharyngeal extension was an independent factor in predicting overall relapse, local relapse, and distant metastasis. Advanced T classification (T3) was another independent factor in predicting overall and local relapse, whereas advanced N classification (N3) was another independent factor in predicting overall relapse and distant metastasis. CONCLUSIONS: Extensive paranasopharyngeal extension (Grade 2/3) was an independent prognostic factor associated with poorer treatment outcome, both in local control and distant metastasis. Ho's T2 disease should be further subclassified into T2a and T2b, which include Grade 0/1 and Grade 2/3 paranasopharyngeal disease, respectively.

Adult↗

The antiemetic efficacy of tropisetron plus dexamethasone as compared with conventional metoclopramide-dexamethasone combination in Orientals receiving cisplatin chemotherapy: a randomized crossover trial.

1. We report a single-blind randomized crossover trial comparing the efficacy of tropisetron plus dexamethasone (TROPDEX) vs conventional combination of metoclopramide, dexamethasone and diphenhydramine (METDEX) in prevention of acute and delayed vomiting in Chinese patients receiving high dose cisplatin. 2. Thirty-six consecutive patients with nasopharyngeal carcinoma were entered into the study, all received cisplatin at a dose range of 60-100 mg/m2. Patients were randomized in the sequence of antiemetic regimens used in two consecutive cycles. 3. The TROPDEX regimen consisting of tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. given on day 1 of chemotherapy, followed by oral maintenance with tropisetron 5 mg daily and dexamethasone 4 mg twice daily from day 2 to 6. The METDEX regimen consisting of metoclopramide 1 mg kg-1 i.v., dexamethasone 20 mg i.v. and diphenhydramine 25 mg i.v. given before chemotherapy and then 2 hourly for two more doses on day 1, followed by oral metoclopramide 20 mg 6 hourly from day 2 to 6. 4. Complete control of acute vomiting was observed in 64% of patients with TROPDEX as compared with 14% with METDEX (P < 0.01). While complete plus major control of acute vomiting was observed in 84% with TROPDEX as compared with 58% with METDEX. The mean vomiting episodes on day 1 were 1.4 with TROPDEX as compared with 3.5 with METDEX (P < 0.01). There was, however, no significant difference between the two regimens in the control of delayed vomiting. 5. When patients randomized to TROPDEX in the second cycle were compared with those with TROPDEX in the first cycle, the antiemetic efficacy was reduced, with mean acute vomiting episodes of 2 in the former compared with 0.8 in the latter (P < 0.01). 6. The most common adverse effect observed was headache in TROPDEX (27%) and dizziness in METDEX (40%). 7. In conclusion, the antiemetic regimen TROPDEX is effective in Chinese patients receiving high dose cisplatin chemotherapy and is well tolerated. It is better than conventional METDEX regimen in the control of acute vomiting, but not in the control of delayed vomiting.

Antiemetics↗

Surgical resection of pulmonary metastases from nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC), unlike other head and neck cancers,is known for its propensity for distant metastases. Chemotherapy remains the mainstay of treatment because of this and the chemosensitivity of the tumour, but long-term control is rare. The surgical management of pulmonary metastases of other extrathoracic malignancies prompted this review of surgical management of patients with NPC. METHODS: Thirteen thoracotomies were performed in 12 patients with pulmonary metastases as the first and only site of relapse of nasopharyngeal carcinoma. Postoperative chemotherapy was given in four patients, radiotherapy to the mediastinum in one patient and both chemotherapy and radiotherapy in two patients. The survival pattern of this group of 12 patients was compared with a historical control group consisting of 65 patients without surgical resection. RESULTS: Lymph node involvement was documented in four patients during operation. Four patients relapsed after surgical resection, two of them were from the group of three patients with lymph node involvement. The site of subsequent relapse was the lung for three patients and the skeletal system for the fourth. The 2 year actuarial survival of the surgically resected group compared favourably with the historical control group (80% and 24.1%, respectively; P=0.0002 by Mantel-Cox text). CONCLUSIONS: Surgical resection of pulmonary metastases from NPC seems to be a promising approach thought the effect of case selection cannot be excluded and further studies are indicated. The importance of exploration and dissection of mediastinal nodes in the surgical management of pulmonary metastases from NPC was demonstrated.

Actuarial Analysis↗

Species differences in the activity of the Na(+)-Ca2+ exchanger in mammalian cardiac myocytes.

1. Species differences in the activity of the exchanger were evaluated in isolated myocytes from rat, guinea-pig, hamster ventricles and human atria. Fluorescence measurements using fura-2 were carried out in conjunction with the whole-cell patch-clamp technique for simultaneous recording of membrane currents and intracellular Ca2+ concentration. 2. Ca2+ release from sarcoplasmic reticulum (SR) induced either by rapid application of caffeine or by Ca2+ current elicited inward Na(+)-Ca2+ exchange currents (INa-Ca). The magnitude of INa-Ca was largest in hamster, smallest in rat, with guinea-pig and human myocytes having intermediate values. The ratio of caffeine-induced exchanger current densities, normalized with respect to the peak Ca2+ release, was 4:2:1.5:1 for hamster > guinea-pig > or = human > or = rat myocytes. 3. The rates of Ca2+ removal in the presence of caffeine, which reflect primarily the Ca2+ extruding activity of the Na(+)-Ca2+ exchanger, followed the same order of hamster > guinea-pig > or = human > or = rat. 4. The kinetics of INa-Ca vs. Ca2+ transients were different among species. In rat myocytes, the kinetics of the INa-Ca and the Ca2+ transients were similar, with INa-Ca linearly proportional to intracellular Ca2+ concentration ([Ca2+]i). In hamster myocytes, the time course of INa-Ca tracked only the declining phase of the Ca2+ transient with INa-Ca having faster kinetics during the Ca2+ release. These findings suggest that the Ca2+ concentrations in the vicinity of the exchanger were significantly higher than those of the cytosol during Ca2+ release in hamster myocytes. 5. We concluded that there are significant species differences in the exchanger activity of cardiac myocytes, arising from differences in exchanger densities, their modulation and/or their spatial distribution with respect to the ryanodine receptors of cardiac myocytes.

Animals↗

Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes.

In skeletal muscle, dihydropyridine receptors are functionally coupled to ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional complexes. In cardiac muscle direct physical or functional couplings have not been demonstrated. We have tested the hypothesis of functional coupling of L-type Ca2+ channels and ryanodine receptors in rat cardiac myocytes by comparing the efficacies of Ca2+ in triggering Ca2+ release when the ion enters the cell via the Ca2+ channels or the Na+/Ca2+ exchanger. Ca2+ transported through the Ca2+ channels was 20-160 times more effective than Ca2+ influx via the Na+/Ca2+ exchanger in gating Ca2+ release from the sarcoplasmic reticulum, suggesting privileged communication between Ca2+ channels and ryanodine receptors. In support of this hypothesis we found that Ca2+ channels were inactivated by Ca2+ release from the sarcoplasmic reticulum, even though the myoplasmic Ca2+ concentrations were buffered with 10 mM EGTA. The data thus suggest privileged cross signaling between the dihydropyridine and ryanodine receptors such that Ca2+ flux through either the Ca2+ channel or the ryanodine receptor alters the gating kinetics of the other channel.

Animals↗

Maxillary swing approach for resection of tumors in and around the nasopharynx.

The efficacy of the anterolateral approach to the nasopharynx and its vicinity was evaluated. Using this maxillary swing approach, we have removed tumors in and around the nasopharyngeal region in 26 patients. Among them, 18 suffered from recurrent primary nasopharyngeal carcinoma after external radiotherapy, three patients had chordoma, two had schwannoma, one had adenocarcinoma of the nasopharynx, and one had malignant fibrous histiocytoma. The last patient had a recurrent deep-lobe parotid gland tumor localized in the paranasopharyngeal space. The facial wounds in all 26 patients healed primarily with no evidence of necrosis of the maxilla. Seven patients developed palatal fistula, five of them subsequently healed, whereas one patient required surgical closure and one had to wear a dental plate. This group of patients was followed up from 4 to 42 months (median, 15 months). Among the 18 patients with recurrent nasopharyngeal carcinoma, five had local recurrence, four died of other conditions, and nine of them are still alive with no evidence of disease. This gives an actuarial control of tumor in the nasopharynx of 42% at 3.5 years. In the eight patients remaining, one died of recurrent chordoma, two are alive with recurrent disease, and five are free of disease. Exposure of the nasopharynx and the paranasopharyngeal space is possible using the anterolateral approach. The associated morbidity is low.

Adenocarcinoma↗

Sacral and pubic insufficiency fractures after irradiation of gynaecological malignancies.

The association between radiotherapy and insufficiency fractures of the pelvis has not been well documented. Fractures were detected over a 2-year period in eight postmenopausal women who had previously undergone irradiation for gynaecological malignancies. Six of these patients also had local soft tissue complications, such as rectal bleeding and haematuria, in addition to severe low back, buttock or groin pain, caused by the fractures. Plain radiographs were unhelpful in the detection of sacral insufficiency fractures, but showed the pubic fractures in five patients. Diagnoses of insufficiency fractures were made on bone scintigraphic demonstration of the typical 'H' shaped sacral pattern, or the combination of the partial 'H' pattern together with public uptake. Computed tomography was useful for confirmation of insufficiency fractures in doubtful cases. Recognition of insufficiency fractures helps to avoid the pitfalls of misdiagnosing tumour recurrence or bony metastases.

Aged↗

Tension pneumocephalus--a rare complication of radiotherapy in nasopharyngeal carcinoma.

A patient with nasopharyngeal carcinoma (NPC) treated by radiotherapy developed tension pneumocephalus due to a naso-cranial fistula. The fistula was due to a pathological fracture at the base of skull affected by bone necrosis. The clinical features, neuro-radiological and post-mortem findings are presented. This is the first case report of pneumocephalus in association with NPC. The brain showed florid subarachnoid and intraventricular air collection under tension, low grade meningitis, foreign body giant cell reaction in the arachnoid membrane and multifocal cerebral infarction. Late radiation necrosis was also found in the left temporal lobe. The cause of the tension pneumocephalus in relation to radiation bone necrosis and the possible role of pneumocephalus in producing the multifocal cerebral infarction are discussed. The more common radiation necrosis of brain is also discussed. The pathogenesis of the pneumocephalus in this patient is distinctly different from the more common causes such as head injury and surgery.

Aged↗

Maxillary osteonecrosis after radiotherapy for nasopharyngeal carcinoma.

A case of extensive osteoradionecrosis of the posterior maxillae, pterygoid plates and floor of the sphenoid sinuses is reported. The patient received more than one full course of radical radiotherapy for nasopharyngeal carcinoma. Although there was complete remission of the tumour, she suffered from repeated episodes of gum bleeding which was found to be due to oroantral fistulas and severe dental decay. The large fraction dose and total dose, severe dental caries and xerostomia are the most likely contributory causes to this unusual complication in our patient.

Adult↗