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Biomedical subjects

J S Sham

Publications and source records attributed to J S Sham.

At least 91 records · Page 5Linked to original sources

Enhanced Na(+)-Ca2+ exchange activity in cardiomyopathic Syrian hamster.

The signaling of contraction by Ca2+ in the Syrian hamster (BIO 14.6) heart in the late stage of the cardiomyopathy (220 to 300 days old) was compared with that in age-matched healthy hamster hearts. Membrane current and cell shortening or intracellular Ca2+ transients were measured simultaneously in isolated whole-cell-clamped myocytes. The density of the L-type Ca2+ current was smaller in myopathic than in normal myocytes (2.13 +/- 0.3 versus 3.21 +/- 0.4 pA/pF at 0 mV, P < .05). In both control and myopathic myocytes, the L-type Ca2+ current gated the release of Ca2+ and activation of contraction. In myopathic myocytes, activation of contraction also activated a slowly inactivating inward current of 1.73 +/- 0.2 pA/pF. The Na(+)-Ca2+ exchanger generated this current (INa-Ca), because it was suppressed by rapid replacement of Na+ with Li+ and depletion of the intracellular Ca2+ pool by caffeine. INa-Ca, activated by rapid application of caffeine, was not significantly different in both groups (3.7 +/- 0.5 pA/pF in control hearts versus 3.9 +/- 0.5 pA/pF in cardiomyopathic hearts). The activation of the inward exchanger current in myopathic myocytes coincided with a significant prolongation of contraction and the intracellular Ca2+ transient and a delay in the onset of relaxation. These results suggest that the enhanced activity of the Na(+)-Ca2+ exchanger may be related to compromised sequestration of Ca2+ in these animals.

Animals↗

Computed tomography evaluation of neck node metastases from nasopharyngeal carcinoma.

PURPOSE: To study the role of computed tomography in the pre-therapy evaluation of nasopharyngeal carcinoma. METHODS AND MATERIALS: The computed tomography of 119 new patients of nasopharyngeal carcinoma were evaluated independent of clinical findings for neck node metastases, and then compared with clinical findings. Contrast enhanced axial scans were obtained at 5 mm intervals with the infraorbitomeatal line parallel to the gantry. Scans were obtained from the supra-sellar cistern to the C5 or C6 vertebra for the evaluation of the base of skull, nasopharynx, paranasopharyngeal space and the upper and mid neck. RESULT: The present study confirmed the disparity of nodal extent documented by clinical palpation and computed tomography. Of the 37 patients who have no clinically palpable node (N0), computed tomography showed nodal involvement in 11 (29.7%) of them, and they were up-staged from N0 to N1. Computed tomography showed multiple or bilateral nodes in seven (58.3%) of the 12 patients with AJC N1 disease and they were hence up-staged to N2. All together, there were 28 (23.5%) patients who have no computed tomography evidence of nodal involvement by tumor. In agreement with clinical experience, the most commonly involved nodal groups were the upper internal jugular and upper spinoaccessary, followed by the lateral retropharyngeal. The percentage of nodes which were not clinically palpable was roughly the same for different regions (15-30%), except, as expected, that all the retropharyngeal nodes were not palpable. The risk of harboring retropharyngeal node was proportional to the size of the largest node in the ipsilateral neck. CONCLUSION: A significant proportion of patients with clinically negative neck (N0) or AJC N1 disease will be upstaged by computed tomography, thus supporting its routine use in pre-therapy evaluation of nasopharyngeal carcinoma.

Head and Neck Neoplasms↗

Epstein-Barr virus carriage by nasopharyngeal carcinoma in situ.

We studied the distribution of the EBV genome in tumour biopsies obtained from 42 patients with poorly differentiated or undifferentiated nasopharyngeal carcinoma (NPC) and 3 patients with well-differentiated NPC. Six carcinoma in situ (CIS) foci were seen in 5 tumour specimens. By in-situ hybridization, multiple copies of the EBV genome were detected in some of the tumour cells in 3 CIS lesions involving the full thickness of the mucosal epithelium, but without microinvasion, while the viral genome was present in the majority of the tumour cells contained in another 3 CIS lesions with microinvasion. In agreement with previous findings, poorly differentiated and undifferentiated carcinomas regularly carried the viral genome, the number of copies of which was similar to that seen in CIS, while some, but not all, of the tumour cells of the well-differentiated histological type carried the virus. The viral genome was otherwise rarely detected in other areas of the mucosal epithelium and, where present, the viral carriage was confined to a few epithelial cells, in which the viral genome contents were markedly lower than in tumour cells. These results suggest that EBV may first become associated with NPC at an early stage of the disease shortly after the tumour has been initiated.

Biopsy↗

Analysis of Epstein-Barr virus in localized nasopharyngeal carcinoma tumors.

BACKGROUND: An f variant of Epstein-Barr virus (EBV) appears associated with nasopharyngeal carcinoma (NPC) in Southern Chinese. Early diagnosis of the tumor allows the detection of some localized tumors. METHODS: A polymerase chain reaction (PCR) assay for genotyping EBV was used to evaluate the presence of the virus in NPC biopsies of local tumors of eight Chinese patients. RESULTS: The f variant was detected in the nasopharynx of seven of eight patients. The f variant was present in equal frequency in the "normal" and tumor regions. CONCLUSIONS: Examination of localized NPC tumors by the PCR genotyping assay revealed EBV was present on the tumor side of the nasopharynx in greater quantities than the "normal" side in seven of eight patients studied. Concurrent infection with both the prototype F and f variant was observed in two of the eight patients investigated.

Carcinoma↗

Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma.

PURPOSE: To evaluate the efficacy of radioactive gold grain implant via the split palate approach in the control of locally recurrent or persistent nasopharyngeal carcinoma. METHODS AND MATERIAL: Forty-three patients, 10 for persistent NPC, 28 for first relapse in the nasopharynx, and five for second relapse in the nasopharynx, were treated. The diameter of the tumors at the time of gold grain implant ranged from 0.5 to 5 cm, the number of gold grains inserted varied from 4 to 14, the median number was seven. RESULTS: There was no significant difference in the control of the primary tumor for persistent disease (80% at 5 years), first relapse (61% at 5 years) and second relapse (80% at 3 years), p = 0.8845. The difference in survival between the three subgroups of patients, however, was highly significant (p = 0.0040). Thirty patients had CT evaluation before gold grain implant and the tumor was found confined to the nasopharynx in 21, in the remaining nine patients erosion of the sphenoid sinus or other parts of the base of skull was noted. The difference in the control between those patients with tumors confined to the nasopharynx and those patients with extranasopharyngeal extension of tumor almost reached statistical significance (81% and 44% respectively at 5 years, p = 0.0554). For the six patients who developed local recurrence after gold grain implant and were evaluable for the pattern of failure, the recurrent tumors were considered originating from another region of the nasopharynx in four, and in-field failure in the other two cases. CONCLUSION: Radioactive gold grain implant as salvage treatment provides satisfactory control of persistent and recurrent nasopharyngeal carcinoma. The local control was better when the tumor was localized to the nasopharynx, thus underlines the importance of close follow-up for early recognition of relapse and persistent tumor. However, such patients still suffered from high incidence of regional and distant failure, the pathophysiology and management of which require further investigation.

Adult↗

Effects of high-frequency ventilation and PEEP on carotid baroreceptor reflexes.

We tested the hypothesis that altering the pattern and/or magnitude of discharge of pulmonary stretch receptors (PSRs) would alter baroreceptor reflexes in anesthetized aortic-denervated cats. Carotid baroreceptor control of mean arterial pressure (MAP), heart rate (HR), and hindlimb perfusion pressure (PPhl) was examined by changing carotid sinus pressure (CSP) from 50 to 225 mmHg. The pattern of PSR discharge was changed by switching conventional mechanical ventilation (CMV) to high-frequency ventilation (HFV). Magnitude of PSR discharge was altered by changing positive end-expiratory pressure (PEEP). Altering the discharge pattern of PSR had no effect on CSP-MAP or CSP-PPhl relationships; small changes in HR were observed. Increasing PSR activity by increasing PEEP during CMV (from 3 to 9 cmH2O) depressed CSP-MAP relationship, set point, and threshold pressure. However, the depression in CSP-MAP relationship and set point during PEEP was unrelated to PSR activation, because these changes were not abolished after bilateral vagotomy. CSP-PPhl relationship was significantly elevated during PEEP before and after vagotomy, suggesting activation of a nonvagally mediated vasoconstrictory mechanism instead of PSR-mediated depressor reflex. CSP-HR relationship during PEEP showed a slight elevation, which was abolished after vagotomy. We conclude that despite minor increases in HR, altering the pattern of magnitude of PSR activity with HFV and PEEP has no significant effect on carotid baroreceptor regulation of systemic circulation. Hemodynamic changes observed during PEEP were likely due to its mechanical effect on cardiac output and activation of other cardiopulmonary receptors rather than to the increase in PSR activity.

Animals↗

Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study.

METHODS: A prospective, randomized controlled study of radiotherapy after resection of esophageal carcinoma was carried out in 130 patients. Patients were stratified according to whether the resection was curative or palliative and were then randomized to receive postoperative radiotherapy or no additional treatment. Sixty patients underwent curative resection; 30 each were randomized into the radiotherapy group (CR + R) and the control group (CR). Seventy patients underwent palliative resection; 35 each were randomized into the radiotherapy group (PR + R) and the control group (PR). RESULTS: No complications occurred while the patients were undergoing radiotherapy treatment. On follow-up, complications in the intrathoracic stomach occurred in 24 patients (37%) who underwent radiotherapy compared with four patients (6%) in the control group (p < 0.0001). Seventeen of these 24 patients in the radiotherapy group had gastric ulceration and there were five deaths as a result of bleeding. Local recurrence developed significantly less frequently in the PR + R group compared with the PR group (seven patients [20%] vs 16 patients [46%]; p = 0.04); no difference was observed between CR + R and CR groups (10% and 13%, respectively). Intrathoracic recurrence occurred in fewer patients in the radiotherapy groups (CR + R and PR + R) compared with the control groups (CR and PR) (four patients vs 15 patients; p = 0.01). In patients with residual tumor in the mediastinum after resection, two (7%) of 29 patients who underwent radiotherapy died of tracheobronchial obstruction, compared with nine (33%) of 27 patients in the control groups (p = 0.03). No difference in local recurrence was observed for extrathoracic or anastomotic recurrence. Distant metastasis developed in 12 patients (40%) in the CR + R group, nine patients (30%) in the CR group (p = 0.59), 24 patients (69%) in the PR + R group, and 18 patients (51%) in the PR group (p = 0.22). The time of onset of metastasis was 5.1 months for the PR + R group, which was shorter than the 8.5 months for the PR group (p = 0.05). The time of onset of metastasis was similar for the CR + R and CR groups (9.9 months and 11.0 months, respectively; p = 0.76). The overall median survival of patients after postoperative radiotherapy (CR + R and PR + R) was 8.7 months, which was shorter than the 15.2 months for the control groups (CR and PR) (p = 0.02). CONCLUSIONS: The shorter survival of patients who underwent postoperative radiotherapy was the result of irradiation-related death and the early appearance of metastatic diseases. The role of postoperative radiotherapy is therefore limited to a specific group of patients with residual tumor in the mediastinum after operation, for whom radiotherapy can significantly reduce the incidence of local recurrence obstructing the tracheobronchial tree.

Adenocarcinoma↗

Extent of nasopharyngeal carcinoma involvement inside the nasopharynx. Lack of prognostic value on local control.

A study on the use of fiberscopic examination and multiple biopsy specimens taken from the nasopharynx in the assessment of the extent of nasopharyngeal carcinoma (NPC) involvement inside the nasopharynx found that the involvement often was more extensive than the detected with conventional methods. In the current study, 247 patients with NPC were studied with the use of fiberscopic examination, and multiple biopsy specimens were taken from the superior wall, posterior wall, and lateral wall of the nasopharynx on both sides. It was confirmed that the tumor often involved the nasopharynx extensively. Also, the extent of primary tumor involvement inside the nasopharynx was correlated with the American Joint Committee (AJC) T stage and the degree of paranasopharyngeal extension of the tumor (P = 0.0100 and 0.0009, respectively), as well as with the size of the largest node and the lowest neck level involved by the node in the ipsilateral neck (P = 0.0005 and 0.005, respectively). However, the extent of primary tumor involvement inside the nasopharynx, expressed as either the number of the six standard sites or the number of the AJC subsites that were involved, had no predictive value on the control of the primary tumor (P = 0.3773 and 0.7794, respectively) at a median follow-up time of 27 months. Except when salvage brachytherapy is contemplated for persistent or recurrent NPC, the extent of primary tumor involvement inside the nasopharynx should not be routinely studied.

Actuarial Analysis↗

Gating of the cardiac Ca2+ release channel: the role of Na+ current and Na(+)-Ca2+ exchange.

In cardiac myocytes, calcium influx through the calcium channel is the primary pathway for triggering calcium release. Recently it has been suggested that the calcium-induced calcium release mechanism can also be activated indirectly by the sodium current, which elevates the sodium concentration under the cell membrane, thereby favoring the entry of "trigger" calcium via the sodium-calcium exchanger. To test this hypothesis, sodium current was suppressed by reducing the external sodium concentration or applying tetrodotoxin. At potentials positive to -30 millivolts, calcium release was unaffected. A small calcium release at more negative potentials could be attributed to partial activation of calcium channels, because it was unaltered by replacement of sodium with lithium and was blocked by cadmium. Thus, sodium influx or its accumulation does not initiate calcium release. In addition, sodium-calcium exchange-related calcium release at potentials positive to +80 millivolts has slower kinetics than calcium channel-induced release. Therefore, only the calcium channel gates the fast release of calcium from the sarcoplasmic reticulum in the range of the action potential.

Animals↗

Immunoglobulin A against viral capsid antigen of Epstein-Barr virus and indirect mirror examination of the nasopharynx in the detection of asymptomatic nasopharyngeal carcinoma.

To evaluate the efficacy of population screening for early stage nasopharyngeal carcinoma (NPC) in southern China, the authors recruited 42,048 and 10,402 apparently healthy subjects residing in a high incidence and a low incidence area, respectively; all subjects were between the ages of 30 and 59 years. The subjects' serum specimens were tested for immunoglobulin (Ig) A antibody against viral capsid antigen (IgA/VCA) of Epstein-Barr virus (EBV). Of the subjects from the high incidence area, 2823 were found to be seropositive. In follow-up, they had yearly examinations of the nasopharynx by indirect mirror with or without biopsy; 41 were found to have histologically confirmed asymptomatic NPC during the first 2 years of follow-up. The tumors in most of these cases were localized and were at earlier stages than tumors of symptomatic cases of NPC seen in the same region before the screening. The yearly indirect mirror examination of the nasopharynx seems to have effectively identified most of the tumors at the stage of asymptomatic disease. The risk of harboring NPC was found to be different among the different sex and age subgroups of seropositive individuals. By limiting such screening to those who are at exceedingly high risk, the cost of the screening can be kept within the spending of the public health authority, and the effectiveness of the screening also is improved.

Adult↗

Serous otitis media. An opportunity for early recognition of nasopharyngeal carcinoma.

In a prospective study of 271 new patients with nasopharyngeal carcinoma, 36 (13.3%) were found to have cranial nerve involvement. Serous otitis media (SOM) was found in 98 (41.4%) of 237 patients who had undergone complete otologic assessment. The local control of tumor and actuarial survival of three subgroups of patients, namely, 80 patients with SOM only, 11 patients with cranial nerve palsy only, and 18 patients with both SOM and cranial nerve palsy, were analyzed. The local control of tumor was better in patients with SOM alone than in those with cranial nerve palsy alone; those patients with both SOM and cranial nerve involvement had worse local control as well as survival. As SOM is not uncommon in the diagnosis of nasopharyngeal carcinoma, and adult-onset SOM is otherwise distinctly uncommon, this provides a good opportunity for early recognition and, perhaps, better control of nasopharyngeal carcinoma.

Actuarial Analysis↗

Transcription of BamHI-A region of the EBV genome in NPC tissues and B cells.

Analysis by Northern blotting and sequencing of cDNA clones from a transcription library of a tumor biopsy from a nasopharyngeal carcinoma (NPC) patient showed that the BamHI-A region of the Epstein-Barr virus genome is abundantly and regularly transcribed in tumor tissues from NPC patients. The transcription occurred in a rightward direction terminating between coordinates 160,965 and 160,995, where two polyadenylation sites are located. Rightward transcription of this region also occurred in B lymphoid cells harboring the viral genome, albeit at a lower level than in the tumor tissues. Differential splicing yields a family of related transcripts displaying at least four splicing patterns. Different promoters may be utilized, further contributing to the diversity of this family of transcripts. A 2.8-kb unspliced transcript present in B95-8 cells was probably initiated from a TATA box located in position 158,204, while the other transcripts may utilize other promoters localized to other regions. All the transcripts encompass a putative open reading frame, BARFO, which is predicted to encode a basic protein of about 20 kDa. It shares 40% colinear amino acid sequence homology with the DNA binding region of a transcription factor, ICP4, specified by herpes simplex virus.

Amino Acid Sequence↗

Computed tomography of paranasopharyngeal spaces: normal variations and criteria for tumour extension.

In 137 normal CT scans of the nasopharynx, the parapharyngeal spaces at the nasopharynx level were asymmetrical in 30%. Their difference in width and distance from the midline was greater than 1 mm in 51% and 44% respectively. Fat was absent in the interpterygoid fascia in 20%, in the alar fascia in 28%, in the prevertebral space in 35%, and in the retropharyngeal space in 99% of patients. Assessment of tumour extension to the paranasopharyngeal space usually relies on symmetry and fascial fat planes. As either feature may not be present in the normal person, the relation of the tumour to two lines representing two fascial planes is proposed as a complementary method for the evaluation of tumour extension.

Adipose Tissue↗

Infratemporal pneumatocele arising from maxillary sinus.

Pneumatocele of the infratemporal fossa caused by herniation of air through a break in the wall of the aerated maxillary sinus is rare. Two cases are reported: one arising from a maxillary pneumocele with a defect in the wall of the zygomatic recess and one associated with maxillary radionecrosis with pathological fracture complicated by infection. Computed tomography can clearly demonstrate the extent of the pneumatocele, and can show the maxillary pathology and the causative bony defect in the sinus. Treatment depends on the clinical conditions of the patient, the pathology and the size of the bony defect.

Adult↗

Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma--a prospective study.

A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway.

Adult↗

Nasopharyngeal carcinoma in situ in nasopharyngeal carcinoma.

AIMS: To assess the presence of carcinoma in situ (CIS) in patients with nasopharyngeal carcinoma (NPC) and to see if the number of biopsy sites facilitates detection of CIS. METHODS: Formalin fixed, paraffin wax embedded biopsy specimens (n = 285) from 187 patients with NPC in 1987 were studied for the presence of CIS as well as for the histological assessment of the subtype of CIS. RESULTS: Fifteen (8.0%) patients had CIS, representing 8.3% of all new patients with NPC and 11.6% of patients with persistent disease or relapse. CIS was undifferentiated or poorly differentiated, no cases of well differentiated squamous cell CIS were identified. There was no significant difference in the incidence of CIS when multiple endoscopic biopsy specimens were taken rather than single forceps biopsy specimens. CONCLUSIONS: CIS can only be identified in a few patients with NPC largely because of late presentation with advanced disease at the time of diagnosis and the focal nature of the dysplastic process. The presence of dysplasia in relapses of NPC suggests that these tumours may be second growths rather than regrowths of a primary tumour.

Carcinoma in Situ↗

Peripheral chemoreceptor modulation of the pulmonary vasculature in the cat.

The present study was undertaken to determine whether stimulation of the carotid and aortic bodies (cb and ab) could affect the pulmonary vasculature. Our hypothesis was that each promoted vasodilation and thus could modulate the pulmonary vasoconstrictor response to hypoxia. The experimental design of the first set of experiments took advantage of the facts that 1) the ab, but not the cb, increases its neural output in response to CO, whereas both respond to a decreased arterial PO2 (hypoxic hypoxia, HH) and 2) the aortic nerves in cats are easily transected. Hence, both cb and ab sent neural activity to the brain stem when the intact cat was exposed to 10% O2 in N2. Only the ab sent information during CO hypoxia (COH intact). Only the cb did so during HH in the cat in which the aortic nerves had been transected, removing the aortic body (HH abr); neither ab nor cb did so during COH abr. Fifteen anesthetized paralyzed artificially ventilated cats were fit with catheters in the femoral artery and vein, right and left atria, left ventricle, and pulmonary artery and with an aortic flow probe. In the HH intact and HH abr conditions, there was a significant rise in cardiac output, whereas pulmonary arterial pressure (Ppa) rose initially but then leveled off while cardiac output continued to rise. During the 15-min exposure to HH, pulmonary vascular resistance [PVR = (Ppa - Pla)/cardiac output, where Pla is left atrial pressure] rose initially and then decreased significantly at 2-3 min. In response to COH, PVR showed only a significant decrease. In the second set of experiments, seven cats were instrumented as above and had loops placed in the common carotid arteries for selectively perfusing the cbs. In response to a brief infusion of venous blood mixed with 0.3-0.5 micrograms NaCN, which selectively stimulated only the cb, aortic flow remained relatively constant while heart rate and Ppa - alveolar pressure difference decreased significantly; so also did PVR. These data are consistent with the hypothesis that stimulation of the ab and cb singly or together can provoke a significant pulmonary vasodilation in the anesthetized paralyzed artificially ventilated cat.

Animals↗

Cranial nerve involvement and base of the skull erosion in nasopharyngeal carcinoma.

In a prospective study of 262 consecutive patients with nasopharyngeal carcinoma (NPC), using computed tomography (CT) as their baseline evaluation, erosion of the base of the skull and intracranial extension into the middle cranial fossa were found in 31.3% and 12.2% of patients, respectively. Thirty-four of these patients had cranial nerve involvement at presentation; 30 of them had involvement of one or more of the third to sixth cranial nerves. Most cases of intracranial extension of tumor were accompanied by erosion of the base of the skull, but the reverse was not true. All patients with cranial nerve palsy involving the third to sixth cranial nerves had associated erosion of the ipsilateral base of the skull. The CT evaluation of patients with cranial nerve involvement who are believed to harbor NPC should include thin cuts of the base of the skull for detection of subtle bone erosion. This may be the only clue to the presence of a small NPC. The prognostic significance of cranial nerve involvement, base of the skull erosion, and intracranial extension of the tumor on the survival of the group of 84 patients who had T4 tumors was evaluated with regression analysis using the Cox model. Only cranial nerve involvement was found to be a significant factor influencing survival.

Cranial Nerve Neoplasms↗