Biomedical subjects

C K Ho

Publications and source records attributed to C K Ho.

At least 19 recordsLinked to original sources

PubMed2006

Moderate to severe obstructive sleep apnoea patients is associated with a higher incidence of visual field defect.

PURPOSE: To compare the visual fields (VFs) and optic nerve head changes between obstructive sleep apnoea (OSA) in normotensive patients and an age-matched non-OSA population. DESIGN: Case-control study. PARTICIPANTS: A total of 41 ethnic Chinese patients diagnosed with moderate to severe OSA referred from the Sleep Laboratory, ENT Department, Tuen Mun Hospital. A total of 35 age-matched non-OSA subjects recruited from the Ophthalmology Department, North District Hospital. METHODS: Comprehensive ophthalmological and systemic history, complete ophthalmological examination, including central-30 computerized perimetry for all studied patients. MAIN OUTCOME MEASURES: Polysomnographic data, VF indices, optic disc changes. RESULTS: In the OSA arm, VF indices were significantly subnormal and the incidence of suspicious glaucomatous disc changes was four times higher than that of the control arm. None of the studied patients suffered from any form of anterior segment complications. CONCLUSIONS: Moderate to severe OSA is associated with a higher incidence of VF defect and glaucomatous optic nerve changes.

Adult↗

PubMed2006

Review of first year result of photodynamic therapy on age-related macular degeneration in Chinese population.

PURPOSE: To evaluate the effect of verteporfin therapy (Visudyne) on age-related macular degeneration (AMD) in Chinese patients. The baseline characteristic and the visual outcome will be compared with the treatment of AMD with photodynamic therapy study (TAP) and verteporfin in photodynamic therapy study (VIP). DESIGN: Retrospective comparative case series. METHOD: We recruited patients >50 years old, with best-corrected visual acuity >20/200 and fluorescein angiography documenting subfoveal either predominantly classic with greatest linear dimension <5400 mum or pure occult choroidal neovascularization (CNV) secondary to AMD. We applied non-thermal laser to the lesion 15 min after visudyne infusion as described in TAP study. Patients were followed up with fluorescein angiography every 3 months. Additional treatment would be offered if there was evidence of recurrence of CNV. OUTCOME MEASURE: Baseline characteristic and visual outcome. RESULT: In all, 46 eyes of 42 patients were enrolled at our centre from July 2002 to June 2003. They comprised 11 eyes with predominantly classic lesions and 35 eyes with pure occult lesion. The mean number of treatment sessions given was 2.9 in the first year. At the 12-month examination, there were 63 and 29% of patients showing visual improvement in predominantly classic and occult groups, respectively, while there were only 16% of patients in the TAP study and 12% of patients in the VIP study showing visual improvement in the same period. CONCLUSION: Verteporfin therapy for subfoveal CNV is beneficial to Chinese patients with AMD at first year. The visual result seems to be better than that observed in Caucasian patients.

Aged↗

PubMed2006

Atypical mycobacterial cutaneous infections in Hong Kong: 10-year retrospective study.

OBJECTIVE: To review the epidemiology of atypical mycobacterial cutaneous infection in Hong Kong. DESIGN: Retrospective study. SETTING: Social Hygiene Service (Dermatology Division), the largest dermatological referral centre in Hong Kong. PATIENTS: Patients with a diagnosis of atypical mycobacterial cutaneous infection based on clinical features, histopathology, with or without a positive culture during the period 1993 to 2002. MAIN OUTCOME MEASURES: Epidemiological data, clinical features, histology, microbiological investigation, and treatment response. RESULTS: Of 345,394 dermatological cases presented over the 10-year period, 33 (0.0096%) cases (19 male, 14 female) of atypical mycobacterial cutaneous infection were diagnosed. The most common type of infection was caused by Mycobacterium marinum (n=17, 51.5%), followed by Mycobacterium avium-intracellulare (n=3, 9.1%) and Mycobacterium chelonae (n=2, 6.1%). The upper limb, especially the hands and fingers, was the most common (69.7%) site of involvement. Tissue culture was positive in 18 (54.5%) cases. All biopsies showed granulomatous histology. Thirty-two patients received treatment and 31 responded. Twenty-six were treated with oral tetracycline group of antibiotics (minocycline, doxycycline, tetracycline). The duration of treatment ranged from 8 to 54 weeks (mean, 24 weeks). Mild transient adverse effects to treatment were reported in six cases. CONCLUSION: Atypical mycobacterial infection is rare in Hong Kong. Because of the low sensitivity of traditional culture techniques, atypical mycobacterial infection may be underdiagnosed if only culture-confirmed cases are included. Polymerase chain reaction provides a rapid and sensitive method to improve diagnostic accuracy. Tissue culture is crucial to determine antimicrobial susceptibility. In our study, tetracycline group of antibiotics, especially minocycline, was an effective treatment, particularly in cases caused by Mycobacterium marinum.

Adult↗

PubMed2006

Epidemiology of leprosy and response to treatment in Hong Kong.

OBJECTIVES: To review the reported trend of leprosy in Hong Kong. DESIGN: Retrospective study. SETTING: Three major leprosy clinics in Hong Kong. PATIENTS: Leprosy patients registered between 1970 and 2004. MAIN OUTCOME MEASURES: Incidence, rate of deformities, distribution of leprosy subtypes, age distribution, and relapses after therapy. RESULTS: The incidence of leprosy has decreased from 3.2 per 100,000 population in 1970 to 0.088 per 100,000 population in 2004. The proportion of the three subtypes of leprosy has remained roughly equal. There have been 87 relapses within this period with 54 (62%) cases of lepromatous leprosy, 22 (25%) borderline leprosy, and 11 (13%) tuberculoid leprosy. The overall relapse rate was 6.7% (0.2 per 100 person-years); this can be subdivided as a relapse rate for multidrug therapy of 3.2% (0.33 per 100 person-years) and for dapsone monotherapy of 8.3% (0.2 per 100 person-years). The mean interval to relapse for multidrug therapy and dapsone monotherapy was 1.83 and 5.8 years, respectively. The mean duration till relapse for patients on dapsone monotherapy was 15.6 years. CONCLUSION: Treatment with recommended WHO-multidrug therapy is effective and well tolerated. Dapsone monotherapy is no longer effective. Leprosy is well controlled in Hong Kong but continued surveillance is required to detect relapses and to ensure good patient compliance with treatment.

Clofazimine↗

PubMed2006

Cutaneous tuberculosis in Hong Kong: an update.

OBJECTIVE: To provide an update on cutaneous tuberculosis in Hong Kong. DESIGN: Retrospective study. SETTING: Social Hygiene Service (Dermatology Division), the largest dermatological referral centre in Hong Kong. PATIENTS: Patients presented with cutaneous tuberculosis between 1993 and 2002 inclusive. Case notes, histology reports, and microbiological reports were reviewed with particular reference to the epidemiology, duration of illness, history of contact with tuberculosis, culture results, and response to treatment. RESULTS: There were 147 patients with cutaneous tuberculosis; among these a few had true cutaneous tuberculosis (n = 16) and the remainder were tuberculids (n = 131). In all they accounted for 0.04% of new dermatology cases diagnosed. Cases of cutaneous tuberculosis were distributed as follows: lupus vulgaris (n = 6, 4%), tuberculosis verrucosa cutis (n = 6, 4%), tuberculosis of the skin unclassified (n = 2, 1%), and orificial tuberculosis (n = 2, 1%). Culture and polymerase chain reaction was positive in less than half of the latter cases. All responded well to anti-tuberculosis therapy. Erythema induratum was the most common form (n = 127, 86%), but papulonecrotic tuberculids (n = 4, 3%) were uncommon. Erythema induratum affected the lower limb in all patients, with a female predominance, and responded to isoniazid monotherapy, multidrug anti-tuberculosis therapy, or doxycycline. CONCLUSION: Lupus vulgaris and tuberculosis verrucosa cutis remain the commonest forms of true cutaneous tuberculosis, and erythema induratum is the most common tuberculid. Culture and polymerase chain reaction are positive in a small proportion of patients.

Adult↗

PubMed2005

Shallow ablations in phototherapeutic keratectomy: long-term follow-up.

PURPOSE: To evaluate the long-term efficacy and safety of shallow ablations in phototherapeutic keratectomy (PTK) in patients with recurrent corneal erosions. SETTING: Department of Ophthalmology, Tuen Mun Hospital, Hong Kong, China. METHODS: A retrospective analysis of 13 consecutive eyes with recurrent corneal erosions treated by PTK from 1997 to 1999 was performed. All eyes failed to respond to conventional treatments, and all eyes had corneal erosions involving the visual axis. Outcome measures included number of recurrences, change in best corrected visual acuity (BCVA) and spherical equivalent (SE), and complications arising from the laser treatment. RESULTS: Indications for PTK were recurrent corneal erosions secondary to minor abrasive trauma (9 eyes) and map-dot-fingerprint corneal dystrophy (4 eyes). The mean ablation depth was 4.6 microm (range 3.4 to 5.8 microm). Mean postoperative follow-up was 49.5 months (range 24 to 68 months). The overall success rate after only 1 treatment was 84.6%. Eleven of 13 eyes had a preserved or improved BCVA, while 2 eyes showed deterioration of 1 line on Snellen testing. Seven of 13 patients had no change in SE; the rest had a change of less than +/-0.50 diopters. There were no major complications. CONCLUSIONS: The comparable success rate after a single treatment suggests that PTK may still be effective at a shallower depth than previously considered. Shallow ablations may have lower chances of complications associated with deeper ablations. Further studies involving a larger number of subjects are warranted.

Adult↗

PubMed2005

Mutant p53 melanoma cell lines respond differently to CP-31398-induced apoptosis.

BACKGROUND: p53, a commonly mutated gene in human cancers, participates in cell cycle arrest, DNA repair and apoptosis. A small pharmacological compound, CP-31398, was found to have the ability to promote proper p53 protein folding, activate p53 transcription of downstream targets, and slow tumour growth in mice. Additionally, CP-31398 was found to be able to convert mutant p53 to wild-type conformation in several cell lines. OBJECTIVES: To examine if CP-31398 can revert all mutant p53 proteins to wild-type function. METHODS: We studied a series of apoptotic responses to CP-31398 in three melanoma cell lines varying in p53 mutation status. RESULTS: Upon a moderate dose of CP-31398 treatment (15 microg mL(-1)), only the wild-type p53 MMRU and the single p53 point mutation MeWo cells exhibited apoptosis. Another melanoma cell line, Sk-mel-110, containing multiple p53 mutations, did not exhibit apoptosis. Although CP-31398 enhanced overall p53 protein level, its ability to promote proper folding of p53 protein was limited to CP-31398-sensitive MMRU and MeWo cells. These sensitive cells showed an increased Bax and PUMA transcription, altered mitochondrial membrane potential, followed by the release of cytochrome c, and cleaved caspase-9 and caspase-3. We also demonstrated that Apaf-1 was not involved in CP-31398-mediated apoptosis. CONCLUSIONS: Our results suggest that the ability of CP-31398 to revert mutant p53 proteins to wild-type conformation may be correlated to p53 mutational status. More studies are necessary, to further investigate the effect of CP-31398 on mutant p53 and its potential applications as an anticancer agent.

Apoptosis↗

PubMed2003

Mirizzi syndrome: a diagnostic and operative challenge.

INTRODUCTION: Mirizzi syndrome (MS) is an unusual complication of gallstone disease. The majority of cases are not identified pre-operatively, despite advances in imaging techniques. MATERIALS AND METHODS: Eighteen cases of MS were treated between January 1997 and April 2002. The clinical presentation, modes of investigation, surgical management and outcome are retrospectively reviewed. RESULTS: There were 13 female and 5 male patients, with a mean age of 60 years. Seven patients presented with the classical Charcot's triad. Ultrasonography (US) was the first imaging investigation in 13 patients and computerised tomography (CT) in the other five cases. Eleven patients had a successful endoscopic retrograde cholangio-pancreatography (ERCP) carried out. Diagnosis of MS was arrived at in seven patients following pre-operative imagings. Overall, 11 patients had Type 1 and seven patients had Type 2 MS. In the group with Type 1 MS, nine patients underwent open cholecystectomy, of whom six had concomitant common bile duct (CBD) exploration for stones and one patient with biliary stenosis had a hepaticojejunostomy bypass. Laparoscopic cholecystectomy was attempted in two patients, with successful completion in one case. In the group with Type 2 MS, four fistulas were closed surgically, the other three had biliary bypass procedures. CONCLUSION: Mirizzi syndrome is an unusual condition that poses diagnostic and operative challenges to the surgeon. With a judicious approach during dissection and early recognition of its presence, bile duct injury can be avoided. Good outcome can be achieved with an appropriate surgical procedure.

Adult↗

PubMed2003

A controlled study of sleep related disordered breathing in obese children.

BACKGROUND: Unlike the adult sleep related disordered breathing (SDB) patients who are typically obese, the relation between obesity and childhood SDB is not clear. AIMS: To investigate whether obese children are more at risk of obstructive SDB when compared to normal population, and whether this risk is potentiated by the presence of pharyngeal lymphoid tissue. METHODS: Forty six obese children (age 10.8 (SD 2.3) years; BMI 27.4 (SD 5.1)), and 44 sex and age matched normal weight children (age 11.7 (SD 2.1) years; BMI 18 (SD 1.8)) were studied. All children underwent a set of physical examinations (including the upper airways) and sleep studies. RESULTS: The obese children were different from the normal weight children in terms of type (predominantly obstructive), frequency, and severity of respiratory disturbances. Depending on the criteria used, 26% or 32.6% of obese children had SDB; 2.3% of normal controls had OAI > or =1 and 4.5% had RDI > or =5. Presence of SDB was related to presence of tonsils (size >2; range 0-4) (OR 12.67, 95% CI 2.14 to 75.17) and BMI (OR 1.20, 95% CI 1.08 to 1.33). CONCLUSIONS: Results suggest that obese children are at increased risk of obstructive SDB; the presence of any pharyngeal lymphoid tissue enlargement in obese children should therefore be aggressively managed.

Adolescent↗

PubMed2002

Hepatolithiasis--a case series.

INTRODUCTION: Hepatolithiasis is an uncommon entity in Singapore. We reviewed the cases presented to our institution (a 1200-bedded restructured hospital) over a 5-year period. MATERIAL AND METHODS: Twelve cases of hepatolithiasis were treated between December 1995 and July 2000 representing 0.77% of gallstone disease operated on in the same period. The clinical presentation, investigations, treatment and subsequent progress are presented. RESULTS: The patients' ages ranged from 28 to 82 years. There was a male to female ratio of 5:7. All patients had upper abdominal pain at presentation; 10 patients had clinical evidence of cholangitis. Ultrasound was the commonest first line investigation but additional investigations, such as computed tomographic (CT) scan and various forms of cholangiography, were frequently necessary for complete delineation of the biliary disease. The intrahepatic stones were located predominantly in the left lobe of the liver. Parenchymal atrophy was seen in 83% of patients. Two patients underwent a biliary bypass operation only, 5 had a hepatic resection only, and 5 had combined procedures. Follow-up ranged from 4 to 50 months. Postoperative recovery was generally unremarkable. Complications included subphrenic abscess (1 patient), recurrent stricture (1 patient) and recurrent stones (1 patient). One patient had an elevated serum CA 19-9 preoperatively; a small villous adenoma was noted at the biliary stricture in the resected left lateral segment of the liver. There was no operative mortality. CONCLUSION: Hepatolithiasis is uncommon in Singapore. Complete diagnosis requires a combination of imaging modalities. Surgery remains the mainstay of definitive treatment. With adequate treatment, good outcome is possible.

Adult↗

PubMed2002

Cervical necrotising fasciitis consequent to mastoid infection.

We present a case of cervical necrotising fasciitis in a 56 year old man, secondary to a rare mastoid infection. The patient had coexisting diabetes mellitus and hypertension. He was treated with early surgical debridement followed by neck and chest reconstruction and radical mastoidectomy. Aggressive antibiotic therapy and supportive care was given. He recovered well with minimal residual functional deficit.

Fasciitis, Necrotizing↗

PubMed2001

Trypanosoma brucei RNA triphosphatase. Antiprotozoal drug target and guide to eukaryotic phylogeny.

The mRNA capping apparatus of the protozoan parasite Trypanosoma brucei consists of separately encoded RNA triphosphatase and RNA guanylyltransferase enzymes. The triphosphatase TbCet1 is a member of a new family of metal-dependent phosphohydrolases that includes the RNA triphosphatases of fungi and the malaria parasite Plasmodium falciparum. The protozoal/fungal enzymes are structurally and mechanistically unrelated to the RNA triphosphatases of metazoans and plants. These results highlight the potential for discovery of broad spectrum antiprotozoal and antifungal drugs that selectively block the capping of pathogen-encoded mRNAs. We propose a scheme of eukaryotic phylogeny based on the structure of RNA triphosphatase and its physical linkage to the guanylyltransferase component of the capping apparatus.

Acid Anhydride Hydrolases↗

PubMed2001

Risk of betel chewing for oesophageal cancer in Taiwan.

Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other confounders, we found that subjects who chewed from 1 to 495 betel-year and more than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95% Cl = 1.3-10.1) and 9.2-fold risk (95% Cl = 1.8-46.7), respectively, of developing oesophageal cancer, compared to those who did not chew betel.

Adult↗

PubMed2001

An essential function of Saccharomyces cerevisiae RNA triphosphatase Cet1 is to stabilize RNA guanylyltransferase Ceg1 against thermal inactivation.

Saccharomyces cerevisiae RNA triphosphatase (Cet1) and RNA guanylyltransferase (Ceg1) interact in vivo and in vitro to form a bifunctional mRNA capping enzyme complex. Here we show that the guanylyltransferase activity of Ceg1 is highly thermolabile in vitro (98% loss of activity after treatment for 10 min at 35 degrees C) and that binding to recombinant Cet1 protein, or a synthetic peptide Cet1(232-265), protects Ceg1 from heat inactivation at physiological temperatures. Candida albicans guanylyltransferase Cgt1 is also thermolabile and is stabilized by binding to Cet1(232-265). In contrast, Schizosaccharomyces pombe and mammalian guanylyltransferases are intrinsically thermostable in vitro and they are unaffected by Cet1(232-265). We show that the requirement for the Ceg1-binding domain of Cet1 for yeast cell growth can be circumvented by overexpression in high gene dosage of a catalytically active mutant lacking the Ceg1-binding site (Cet1(269-549)) provided that Ceg1 is also overexpressed. However, such cells are unable to grow at 37 degrees C. In contrast, cells overexpressing Cet1(269-549) in single copy grow at all temperatures if they express either the S. pombe or mammalian guanylyltransferase in lieu of Ceg1. Thus, the cell growth phenotype correlates with the inherent thermal stability of the guanylyltransferase. We propose that an essential function of the Cet1-Ceg1 interaction is to stabilize Ceg1 guanylyltransferase activity rather than to allosterically regulate its activity. We used protein-affinity chromatography to identify the COOH-terminal segment of Ceg1 (from amino acids 245-459) as an autonomous Cet1-binding domain. Genetic experiments implicate two peptide segments, (287)KPVSLYVW(295) and (337)WQNLKNLEQPLN(348), as likely constituents of the Cet1-binding site on Ceg1.

Acid Anhydride Hydrolases↗

PubMed2001

The length, phosphorylation state, and primary structure of the RNA polymerase II carboxyl-terminal domain dictate interactions with mRNA capping enzymes.

The carboxyl-terminal domain (CTD) of elongating RNA polymerase II serves as a landing pad for macromolecular assemblies that regulate mRNA synthesis and processing. The capping apparatus is the first of the assemblies to act on the nascent pre-mRNA and the one for which binding of the catalytic components is most clearly dependent on CTD phosphorylation. The present study highlights a distinctive strategy of cap targeting in fission yeast whereby the triphosphatase (Pct1) and guanylyltransferase (Pce1) enzymes of the capping apparatus do not interact physically with each other (as they do in budding yeast and metazoans), but instead bind independently to the phosphorylated CTD. In vivo interactions of Pct1 and Pce1 with the CTD in a two-hybrid assay require 12 and 14 tandem repeats of the CTD heptapeptide, respectively. Pct1 and Pce1 bind in vitro to synthetic CTD peptides containing phosphoserine uniquely at position 5 or doubly at positions 2 and 5 of each of four tandem YSPTSPS repeats, but they bind weakly (Pce1) or not at all (Pct1) to a peptide containing phosphoserine at position 2. These results illustrate how remodeling of the CTD phosphorylation array might influence the recruitment and dissociation of the capping enzymes during elongation. But how does the CTD structure itself dictate interactions with the RNA processing enzymes independent of the phosphorylation state? Using CTD-Ser5 phosphopeptides containing alanine substitutions at other positions of the heptad, we define essential roles for Tyr-1 and Pro-3 (but not Thr-4 or Pro-6) in the binding of Schizosaccharomyces pombe guanylyltransferase. Tyr-1 is also essential for binding and allosteric activation of mammalian guanylyltransferase by CTD Ser5-PO4, whereas alanine mutations of Pro-3 and Pro-6 reduce the affinity for the allosteric CTD-binding site. These are the first structure-activity relationships deduced for an effector function of the phosphorylated CTD.

Alanine↗

PubMed2001

Structure and mechanism of the RNA triphosphatase component of mammalian mRNA capping enzyme.

The 5' capping of mammalian pre-mRNAs is initiated by RNA triphosphatase, a member of the cysteine phosphatase superfamily. Here we report the 1.65 A crystal structure of mouse RNA triphosphatase, which reveals a deep, positively charged active site pocket that can fit a 5' triphosphate end. Structural, biochemical and mutational results show that despite sharing an HCxxxxxR(S/T) motif, a phosphoenzyme intermediate and a core alpha/beta-fold with other cysteine phosphatases, the mechanism of phosphoanhydride cleavage by mammalian capping enzyme differs from that used by protein phosphatases to hydrolyze phosphomonoesters. The most significant difference is the absence of a carboxylate general acid catalyst in RNA triphosphatase. Residues conserved uniquely among the RNA phosphatase subfamily are important for function in cap formation and are likely to play a role in substrate recognition.

Acid Anhydride Hydrolases↗

PubMed2001

Detection of Kaposi sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma.

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) recently has been identified in the bone marrow (BM) dendritic cell of multiple myeloma (MM) patients. However, whether or not KSHV is associated with MM remains controversial because many studies have failed to detect the presence of KSHV DNA sequences in the BM of their MM patients. METHODS: We have assayed for KSHV DNA sequences in the BM biopsy samples from 49 patients with MM and from 8 patients with normal BM, using nested polymerase chain reaction and dot blot analysis. The polymerase chain reaction product of KSHV was further determined by single-strand conformation polymorphism and sequence analyses. RESULTS: KSHV DNA was detectable in 22 of 49 patients (44.9%) with MM but was not detectable in normal BM cells. Single-strand conformation polymorphism and sequence analyses showed that there were interpatient specific mutations. Sixteen out of 22 KSHV DNA sequences belonged to a previously defined subgroup, and the other 6 remain unclassified and may represent distinct strains of KSHV in Taiwan. CONCLUSIONS: Data strongly supported that KSHV infection did exist in the BM of the current study patients with MM. However, the role of KSHV in the pathogenesis of multiple myeloma remains to be determined.

Adult↗

PubMed2001

A yeast-like mRNA capping apparatus in Plasmodium falciparum.

Analysis of the mRNA capping apparatus of the malaria parasite Plasmodium falciparum illuminates an evolutionary connection to fungi rather than metazoans. We show that P. falciparum encodes separate RNA guanylyltransferase (Pgt1) and RNA triphosphatase (Prt1) enzymes and that the triphosphatase component is a member of the fungal/viral family of metal-dependent phosphohydrolases, which are structurally and mechanistically unrelated to the cysteine-phosphatase-type RNA triphosphatases found in metazoans and plants. These results highlight the potential for discovery of mechanism-based antimalarial drugs designed to specifically block the capping of Plasmodium mRNAs. A simple heuristic scheme of eukaryotic phylogeny is suggested based on the structure and physical linkage of the triphosphatase and guanylyltransferase enzymes that catalyze cap formation.

Acid Anhydride Hydrolases↗