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Biomedical subjects

W K Low

Publications and source records attributed to W K Low.

At least 19 recordsLinked to original sources

Isolation and characterization of skin-type, type I antifreeze polypeptides from the longhorn sculpin, Myoxocephalus octodecemspinosus.

The antifreeze polypeptides (AFPs) are found in several marine fish and have been grouped into four distinct biochemical classes (type I-IV). Recently, the new subclass of skin-type, type I AFPs that are produced intracellularly as mature polypeptides have been identified in the winter flounder (Pleuronectes americanus) and the shorthorn sculpin (Myoxocephalus scorpius). This study demonstrates the presence of skin-type AFPs in the longhorn sculpin (Myoxocephalus octodecemspinosus), which produces type IV serum AFPs. Using polymerase chain reaction-based methods, a clone that encoded for a type I AFP was identified. The clone lacked a signal sequence, indicating that the mature polypeptide is produced in the cytosol. A recombinant protein was produced in Escherichia coli and antifreeze activity was characterized. Four individual Ala-rich polypeptides with antifreeze activity were isolated from the skin tissue. One polypeptide was completely sequenced by tandem MS. This study provides the first evidence of a fish species that produces two different biochemical classes of antifreeze proteins (type I and type IV), and enforces the notion that skin-type AFPs are a widespread biological phenomenon in fish.

Amino Acid Sequence↗

Malignancy of the temporal bone and external auditory canal.

A retrospective study of 18 patients with malignant tumors of the external auditory canal and temporal bone was undertaken to gain an Asian perspective of this rare disease. Of these patients, 15 (83%) had squamous cell carcinoma (SCC) and 61% had stage T3 tumors at presentation. The mean age was 56 years (range 38-82 years). Seven (39%) of the 18 patients had radiation-associated tumors (RATs), and all had undergone radiotherapy for treatment of nasopharyngeal carcinoma. The 1-year cumulative recurrence for the RAT group was 100%, but there was no recurrence in the non-RAT group (P = 0.001). In malignancies of the external auditory canal and temporal bone, a different classification and staging system for patients with RATs may be warranted to better guide treatment strategies.

Adult↗

Diagnostic value of Epstein-Barr viral serology in nasopharyngeal carcinoma.

Although Epstein-Barr virus (EBV) IgA serology has been established as an effective marker for nasopharyngeal carcinoma (NPC), it remains unclear how useful or cost-effective it is as a screening test. This article is aimed at establishing how these tests could be used most effectively in the diagnosis of NPC in an otolaryngology outpatient clinic. A total of 111 consecutive patients with NPC and an equal number of control subjects were studied. Forty-seven patients with NPC had early (AJCC stages 1 and 2) and 64 had advanced (stages 3 and 4) disease. A positive early antigen (EA) serology result was found in 81.2% of NPC patients and in none of the controls. Negative EA and viral capsid antigen (VCA) serology results were present in 2.7% of NPC patients and in 46.8% of controls. Negative EA and positive VCA serology results were found in 30.0% of NPC patients with early disease, 7.8% of NPC patients with advanced disease, and 53.2% of controls. Given its high specificity, serology for EA is recommended as a clinically useful screening test. Serology for VCA, although highly sensitive, has an unacceptably high false-positive rate, and its cost-effectiveness as a universal screening test is questionable.

Adenocarcinoma↗

Correlating clinical appearance of nasopharyngeal carcinoma with tumour staging.

Since there is a tendency for nasopharyngeal carcinoma (NPC) to exhibit sub-mucosal spread and endophytic growth, it would be useful to know if NPC remained inconspicuous in the post-nasal space (PNS) even in advanced stages of disease. The aim of this study was to find out if there was a correlation between tumour appearance in the PNS and tumour stage. One hundred and twenty-two consecutive patients with NPC were studied. The appearance of a tumour in the PNS was classified as to whether or not it was obviously malignant-looking (via naso-endoscopy). Tumour stagings were undertaken according to computerised tomography (CT) scan findings. Of the patients studied, 67 (54.9%) had obvious malignant-looking lesions. Tumour appearance was found to correlate with tumour-staging (p = 0.023, chi-squared test). There was, therefore, a tendency for early tumours to present as inconspicuous or innocuous-looking lesions, whereas advanced tumours tended to appear as obvious malignant-looking lesions in the PNS. The clinical significance of these findings is discussed.

Biopsy, Needle↗

Cerebellopontine angle involvement by nasopharyngeal carcinoma.

OBJECTIVE: This article describes a series of patients with nasopharyngeal carcinoma involvement of the cerebellopontine angle and discusses the clinical significance of this entity. SETTING: Tertiary referral center. STUDY DESIGN: Retrospective case study. PATIENTS: Patients who were diagnosed with nasopharyngeal carcinoma with clinical features of cerebellopontine involvement by tumor. INTERVENTIONS: Cerebellopontine involvement by tumor confirmed by computed tomography, magnetic resonance imaging, or both. RESULTS: Patients with this entity either had advanced disease or had been treated previously for advanced nasopharyngeal carcinoma. They had varied clinical features attributable to cerebellopontine involvement, such as sensorineural deafness, dizziness, facial palsy, and facial numbness. CONCLUSIONS: Cerebellopontine angle involvement by nasopharyngeal carcinoma is a difficult entity, both from the diagnostic and therapeutic points of view. In high-risk patients, particularly in patients who were previously treated for advanced nasopharyngeal carcinoma, a high index of suspicion for nasopharyngeal carcinoma involvement of the cerebellopontine angle is warranted when they experience unexplained neurootologic symptoms such as sensorineural hearing loss, dizziness and facial palsy.

Adult↗

Temporal bone tumours in patients irradiated for nasopharyngeal neoplasm.

Radiation-associated tumours are rare complications of radiotherapy. This study seeks to highlight and discuss the clinically challenging problem of radiation-associated tumours (RATs) in the temporal bones of seven patients previously irradiated for nasopharyngeal neoplasm. Seven patients (six males and one female) with radiation-associated temporal bone tumours are presented (five squamous cell carcinomas, one osteogenic sarcoma and one chondrosarcoma). The initial nasopharyngeal disease for which radiotherapy was indicated was nasopharyngeal carcinoma (six patients) and nasopharyngeal lymphoma (one patient). The latency period between radiotherapy and presentation of temporal bone tumours ranged from five years to 30 years with a mean of 12.9 years. All the patients underwent surgical tumour resection. Three patients had post-operative radiotherapy and one patient underwent pre- and post-operative chemotherapy. Two patients died from the disease within three months of treatment with one patient surviving 36 months at the time of writing. One patient died from an unrelated medical condition three months after surgery. With refinement in radiotherapy techniques and the resultant increase in patient survival, there may be more patients with radiation-associated tumours in the future. It remains imperative for clinicians to be vigilant when patients previously irradiated for nasopharyngeal carcinoma present with otological symptoms as the key to the successful management of this condition lies in the early detection and expedient treatment of this difficult disease.

Aged↗

Uncommon otological manifestations of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is significant for the otologist although the nasopharynx is located outside the anatomical confines of the ear. Middle-ear effusion resulting from NPC is well-known. There are however, other less common ear symptoms of NPC that many physicians are not sufficiently aware of. A personal series of patients with NPC presenting with uncommon symptoms relating to the ear is presented. These include NPC presenting as a) haemotympanum b) a peri-auricular mass c) referred sensation to the ear d) blocked ear e) barotrauma f) an ear polyp g) sudden sensorineural hearing loss. These symptoms may pose diagnostic difficulties, resulting in the diagnosis of NPC being delayed. It was concluded that a high index of suspicion for NPC is warranted in high risk patients presenting with unexplained otological symptoms.

Adult↗

Factors contributing to delayed diagnosis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) can be difficult to diagnose. Not only is the post-nasal space (PNS) inaccessible to examination, it is frequently occupied by normal lympho-epithelium which can make differentiation from NPC difficult. Together with its frequent atypical presentation, it is not surprising that the diagnosis is missed or delayed. This is undesirable as the treatment of early NPC carries an excellent prognosis. The aim of this study is to ascertain the extent of the problem of missed or delayed diagnosis and to study the factors responsible. This was a retrospective study of all newly diagnosed patients with NPC from the Singapore General Hospital and treated in the Department of Therapeutic Radiology in the year 1996 (1 January-31 December). A total of 126 patients were studied. Eighteen patients (14.3 per cent) were found to have delayed diagnosis of more than a month. The delay ranged from 1.2 to 25 months (mean 7.2 months). Factors identified which contributed to delayed diagnosis included i) Clinicians not considering a diagnosis of NPC ii) Clinicians suspecting NPC but misled by the results of investigations iii) Patients refusing investigation or defaulting follow-up. Nearly a fifth of patients with NPC had delayed diagnosis. Many of the factors responsible for the delays appear to be preventable by better patient education and counselling, doctors having sharper clinical acumen and skills in NPC diagnosis and the hospital administration having a system of tracking down high risk patients who default.

Clinical Competence↗

Enhancing hearing preservation in endoscopic-assisted excision of acoustic neuroma via the retrosigmoid approach.

Surgeons using the operating microscope are able to make use of numerous landmarks described for the lateral limits of dissection to preserve hearing in acoustic neuroma surgery via the retrosigmoid approach. Similar landmarks for hearing preservation described specifically for the endoscopic-assisted technique, are lacking. By analysing computed tomography (CT) scans of temporal bones, it was observed that to reach within 3 mm of the lateral end of the internal auditory meatus (IAM) via a 3 cm retrosigmoid craniotomy, drilling should be up to about 3 mm medial to the opening of the vestibular aqueduct. It was hypothesized that in surgery, by keeping 3 mm medial to the opening of the vestibular aqueduct, the integrity of inner ear structures would be preserved. This hypothesis was tested in 30 temporal bones and was found to be true. In addition, the lateral end of the IAM up to the transverse crest could be viewed by the 30-degree rigid angled endoscope. This landmark could, therefore, be utilized in the endoscopic-assisted technique to predict the optimal amount of bone to be removed at a stage before the internal auditory meatal dura is opened when the intact dura affords added protection to the meatal contents during drilling. Well designed dural flaps on the posterior petrous bone could be created by making a longitudinal incision not more than 7 mm from the superior border of petrous bone and a transverse incision at least 17 mm from sigmoid. These flaps minimize injury to the endolymphatic sac and protect the cochlear nerve and vasculature that when damaged, may result in hearing loss.

Endoscopy↗

Skin-type antifreeze protein from the shorthorn sculpin, Myoxocephalus scorpius. Expression and characterization of a Mr 9, 700 recombinant protein.

A cDNA clone encoding a presumptive antifreeze protein was isolated from a skin library from shorthorn sculpin, Myoxocephalus scorpius. The clone encodes a 92-residue mature polypeptide (sssAFP-2) without any signal and prosequence, which suggests an intracellular localization. It is the largest alanine-rich, alpha-helical type I antifreeze protein known. A recombinant fusion protein containing an N-terminal-linked His-tag was produced and purified from Escherichia coli. This protein is alpha-helical at 0 degreesC and exhibits significant antifreeze activity. Northern blot and reverse transcription-polymerase chain reaction analyses indicate that sssAFP-2 mRNA has limited tissue distribution and is present in peripheral tissues such as skin and dorsal fin, but is notably absent in the liver. These studies reinforce recent evidence that indicate that the external tissues of cold water marine fishes are major organs for antifreeze protein synthesis and are likely the first line of defense against the threat of freezing.

Amino Acid Sequence↗

Long-term hearing status after radiotherapy for nasopharyngeal carcinoma.

This paper evaluates the hearing status in the long-term, of patients who have had radiotherapy for nasopharyngeal carcinoma (NPC) and also discusses the hearing losses from a disability point of view, which takes into account binaural hearing. Forty patients who have had NPC successfully treated by a single radical course of radiotherapy of 70-80 Gy were studied at 2-12 years (mean 6.2 years) after radiotherapy. Each patient was examined clinically and with a pure-tone audiogram. Averaged hearing thresholds over 0.5, 1.0, 2.0 and 4.0 kHz were evaluated and a value > 30 dB was considered abnormal. The findings were compared with age-matched controls. The median hearing threshold for each ear in NPC patients was found to be 31.9 dB (range 10.0-86.3 dB) and that for controls 17.5 dB (7.5-38.8 dB) (P < 0.0005, Wilcoxon's matched pairs test). In NPC patients, 44 ears (55.0%) had abnormal hearing, of which 17 (21.3%), 5 (6.3%) and 22 (27.5%) ears had predominantly sensori-neural, conductive and mixed hearing losses, respectively. Nineteen ears had middle ear effusions, accounting for the majority of mixed and conductive hearing losses. In terms of individual patients, 8 (20.0%) and 18 (45.0%) patients had abnormal hearing in one year (monaural hearing disability) and both ears (binaural hearing disability), respectively. In conclusion, a substantial proportion of patients who have had radiotherapy for NPC, have hearing disability in the long-term, as compared to normal controls.

Adult↗

Long-term post-irradiation middle ear effusion in nasopharyngeal carcinoma.

This study aimed to find out if there were factors which influenced the development of long-term middle ear effusion (MEE) in patients irradiated for nasopharyngeal carcinoma. Thirty-five patients (70 ears) were studied for 2-8 years (mean 5.5 years) post-radiotherapy. The factors studied were (a) sex (b) age (c) tumour size and (d) presence of pre-radiotherapy MEE. Only the presence of pre-radiotherapy MEE was found to be statistically significant (P = 0.004, Fisher's exact test). Stepwise multiple regression analysis showed the presence of pre-radiotherapy MEE was a predictor of post-radiotherapy MEE with an odds ratio of 0.67. It is postulated that irreversible Eustachian tube dysfunction occurs when the tube which has been damaged by tumour is further damaged by irradiation. This may explain the frequent persistent otorrhea when ventilation tubes are used to treat post-radiotherapy MEE in patients with nasopharyngeal carcinoma. In conclusion, an ear with pre-irradiation MEE was almost seven times more likely to have long-term post-irradiation MEE than an ear without pre-irradiation MEE.

Ear, Middle↗

The contact bleeding sign of nasopharyngeal carcinoma.

BACKGROUND: The nasopharynx has lymphoepithelium frequently resulting in mucosal irregularities. Therefore, it is often difficult by mere inspection to clinically differentiate nasopharyngeal carcinoma (NPC) from normal tissue. The present study aimed to determine if contact bleeding could be used as a reliable sign to help differentiate the two. METHODS: Fifty consecutive Chinese adult patients with mucosal masses in the nasopharynx suspicious of being NPC were studied. Contact bleeding, if present, was elicited with a swab stick and viewed with a nasal endoscope. Each mass was then biopsied and examined histologically. RESULTS: Twenty-one patients were histologically proven to have NPC and all had contact bleeding (sensitivity rate of 100%). Of those patients who did not have NPC, 10 had contact bleeding (specificity rate of 65.5%) but 90.0% of them exhibited signs and/or symptoms of rhinosinusitis. After the rhinosinusitis was successfully treated, the masses either resolved or exhibited no further contact bleeding. CONCLUSIONS: Illiciting contact bleeding on masses in the postnasal space is inexpensive, safe, and easy. In many cases, it helps the clinician decide if certain masses warrant biopsies to exclude NPC.

Adult↗

Pathogenesis of middle-ear effusion in nasopharyngeal carcinoma: a new perspective.

The theory that middle-ear effusion (MEE) associated with nasopharyngeal carcinoma (NPC) is merely the result of tensor veli palatinus destruction is deficient because recent studies have shown that many patients with NPC have MEE but no tensor veli palatinus dysfunction. The present study evaluates the relationship between MEE and Eustachian cartilage erosion by NPC and examines the pathogenesis of NPC-associated MEE from a new perspective. Thirty-five patients with NPC were studied by magnetic resonance scans taken along the lengths of the Eustachian tubes. Twenty-four patients had tumour involvement of both sides of the nasopharynx so that 59 ears were available for study. Eighteen ears had MEE of which 12 had Eustachian cartilage erosion (p < 0.00001), Fischer's Exact Test). In ears with MEE, Eustachian cartilage erosion was frequently but not necessarily associated with tensor veli palatinus destruction. We postulate that altered Eustachian tubal compliance as a result of cartilage erosion by tumour is an important reason why middle-ear effusions develop in patients with NPC.

Adult↗

Hearing disability before and after radiotherapy for nasopharyngeal carcinoma.

This paper evaluates post-irradiation hearing changes in patients with nasopharyngeal carcinoma (NPC) from a disability orientated approach, which takes into account binaural hearing. Newly diagnosed patients with NPC were studied before radiotherapy, and at four to 12 months (mean 9.2 months) after radiotherapy, provided they remained disease-free. Each patient was examined clinically and with pure tone audiograms. Tympanometry was used to confirm middle ear effusion. Averaged hearing thresholds over 0.5, 1 and 2 kHz were evaluated. If abnormal (> 30 dB), the resultant hearing disability was illustrated by a modified Glasgow Plot. Twenty-three males and 10 females completed the study. Middle ear effusions resulted in 39.3 per cent (binaural in two patients) and 33.3 per cent (binaural in five patients) of patients having hearing disability pre- and post-irradiation respectively. No patient had hearing disability as a result of a sensorineural loss. It is recommended that future reporting of post-irradiation hearing changes in patients with NPC, as in middle ear surgery, be considered from a disability-orientated approach.

Adult↗

Middle ear pressures in patients with nasopharyngeal carcinoma and their clinical significance.

There is a paucity of studies investigating middle ear pressures (MEPs) in patients with nasopharyngeal carcinoma (NPC). This paper prospectively examines MEPs in patients with nasopharyngeal carcinoma before and after radiotherapy and discusses their clinical significance. Newly diagnosed patients with nasopharyngeal carcinoma were studied before and at three to 12 months (mean 7.5 months) after radiotherapy. MEPs were measured by tympanometry. Thirty-three patients completed the study. The mean MEP before and after radiotherapy was -55.2 mm water (range -250 to 45 mm water) and -73.1 mm water (range -215 to 35 mm water) respectively. About two-thirds of assessable ears had an increase in negative MEPs after irradiation and the rest had less negative MEPs after irradiation. Those ears which developed post-irradiation middle ear effusions were found to have pre-irradiation negative middle ear pressures of at least -45 mm water. These findings provide possible explanations for some unexplained audiometric observations previously made in patients with nasopharyngeal carcinoma after radiotherapy. Tympanometry before radiotherapy may prove to be useful in identifying ears with a high risk of developing post-irradiation middle ear effusion.

Adult↗