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Biomedical subjects

J S Sham

Publications and source records attributed to J S Sham.

At least 19 recordsLinked to original sources

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

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

The efficacy of fiberoptic endoscopic examination and biopsy in the detection of early nasopharyngeal carcinoma.

Fiberoptic endoscopic examination and biopsy of the nasopharynx was done in 130 patients as a prospective study. They all had elevated titers of antibodies against the viral capsid antigen of Epstein-Barr virus but no symptoms or signs of nasopharyngeal carcinoma. Each underwent a biopsy from six fixed sites in the nasopharynx. Of the 780 biopsy specimens taken from seven patients, 11 showed the presence of nasopharyngeal carcinoma. Techniques to improve the yields of such biopsies with fiberoptic endoscopy are discussed. The presence of tumor was unrelated to the macroscopic endoscopic findings. The highest incidence of subclinical tumor is in the pharyngeal recess.

Adult

Role of bone scanning in detection of subclinical bone metastasis in nasopharyngeal carcinoma.

One hundred thirty-two new patients with nasopharyngeal carcinoma and no evidence of distant metastases were evaluated for bone metastases with bone scanning. Forty-four patients had abnormal hypercaptation. These abnormal findings were considered related to benign diseases in 39 patients after correlating clinical examinations and skeletal radiographs. The remaining five patients had positive bone scanning which was suggestive of bone metastasis. There were 13 patients who developed symptomatic bone metastases over a follow-up period of 0.2-41 months. In three of these, the bone metastases corresponded to the sites of abnormal hypercaptation in the initial positive bone scanning. In view of the low sensitivity and specificity of bone scanning in this setting, routine bone scanning for staging nasopharyngeal carcinoma is not recommended. But in the research setting, baseline scanning is useful to make subsequent scanning more valuable, and it reduces false-positive results.

Bone Neoplasms

The cytological diagnosis of nasopharyngeal carcinoma using a silk swab stick.

A prospective study was carried out to investigate the efficacy of exfoliative cytology for the diagnosis of nasopharyngeal carcinoma. Exfoliated nasopharyngeal cells were collected from patients with a clinical suspicion of carcinoma by scraping the nasopharyngeal mucosa with a piece of silk wrapped around one end of a wooden stick. Ninety-eight patients were investigated in this manner, and the results of cytological investigation compared with the histological findings. The sensitivity of cytological investigation was 71% and the overall accuracy was 86%. The combined use of cytology and serology as a method of screening for nasopharyngeal carcinomas is discussed.

Adolescent