2009

Fong CB, Thong MK, Sam CK, Mohamed Noor MN, Ariffin R
Correspondence: Ms Fong Cheng Boon c/o Prof Thong Meow Keong, thongmk@um.edu.my

ABSTRACT
Introduction Rett syndrome (RS) is a severe neurodevelopmental disorder characterised by normal neurological development followed by progressive developmental regression. The X-linked dominant inheritance of RS has been mapped to the gene that encodes the methyl-CpG-binding protein-2 (MECP2) at Xq28. In the present study, denaturing high-performance liquid chromatography (DHPLC) was used to detect mutations in the MECP2 gene in 20 Malaysian RS patients.
Methods Polymerase chain reaction (PCR) was carried out to amplify the MECP2 coding exons 2, 3, and 4 in a total of eight reactions (exons 2, 3a, 3b, 4a, 4b, 4c, 4d and 4e). Subsequently, PCR products were analysed by DHPLC.
Results Mutations in the MECP2 gene were detected in 13 of the 20 (65 percent) RS patients. 11 patients had mutations in exons 3b and 4a and six patients had mutations in exon 4c. These mutations were mainly concentrated in the methyl-CpG-binding domain and the transcriptional-repression domain.
Conclusion Through the use of post-PCR high-performance liquid chromatography, 65 percent of 20 RS patients were found to have mutation(s) in the MECP2.

Keywords: denaturing high-performance liquid chromatography, MECP2 mutation, methyl-CpG-binding domain, mutation analysis, Rett syndrome, transcriptional-repression domain
Singapore Med J 2009; 50(5): 529-533

Ngeow WC, Aljunid ST
Correspondence: Dr Ngeow Wei Cheong, ngeowy@um.edu.my

ABSTRACT
Introduction This study was undertaken to establish the craniofacial anthropometric norms of young adult Malaysian Malays.
Methods The study group consisted of convenient samples of 100 healthy volunteers (aged 18–25 years), with an equal number of female and male subjects who had no history of mixed racial parentage. 22 linear measurements were taken twice from 22 landmarks over six craniofacial regions.
Results The Malays shared many similar sizes of measurements with the Singaporean Chinese. Their left eye fissure length and mouth width (ch-ch) were almost identical for both genders. However, Malay females had an upper lip height (sn-sto) (left) and ear width (pra-pa) similar to Singaporean Chinese females. Six other measurements, viz. the head width (eu-eu), head circumference (on-op), face height (n-gn), lower face height (sn-gn), (left) eye fissure height (ps-pi), cutaneous upper lip height (sn-ls) and cutaneous upper lip height (ls-sto), were 0.4–4.3 mm less in the Malays. Measurements for another four parameters, viz. the length of the head (g-op), biocular width (ex-ex), lower vermillion height (sto-li) and (left) ear length (sa-sba), were 0.5–3.6 mm higher in the Malays. Only three measurements were obviously different; the height of the head (v-n) and intercanthal width (en-en), were lower, and the protrusion of the nasal tip (sn-prn) was higher in the Malays.
Conclusion These findings suggest that three features, i.e. the height of the head (v-n), intercanthal width (en-en) and protrusion of the nasal tip (sn-prn) may be useful in differentiating a Malay face from a Singaporean Chinese one.

Keywords: anthropometry, craniofacial anthropometric norms, face, facial features
Singapore Med J 2009; 50(5): 525-528

Saleem MM
Correspondence: Dr Mohammad M Saleem, mohomari@hotmail.com

ABSTRACT
Introduction The aim of the study was to look into the feasibility, safety, efficacy and cost-effectiveness of utilising the remains of central venous catheters in infants from a developing country.
Methods Between June 2005 and December 2006, 96 neonates and infants with various illnesses and required the insertion of central venous access, were divided into two groups; those who required it for a short to medium term (44patients) received a piece of the remains of catheters, and those who required conventional catheter insertion intended for long-term use (52 patients) received a regular catheter. The same principle of insertion was used as for regular central venous access. The external jugular vein was used when possible or the internal jugular vein was used otherwise. After appropriate insertion, the catheter was mounted on an appropriately-sized cannula .A three-way stopcock connection was used to minimise manipulation of the cannula. Postoperative care was the same as for routine central venous lines. Complications encountered in the two groups were recorded and analysed.
Results Of the short- and medium-term catheters, 32 out of 44 patients (72.7 percent) completed the intended course of treatment successfully, and of the long-term catheters, 42 out of 52 patients (80.8 percent) completed the treatment successfully. Recorded complications were dislodgement, thrombosis and infection. These were, in the short-term group, as follows: five (11.4 percent), three (6.8 percent) and four (9.1 percent), respectively; and for the long-term group, two (3.8 percent), four (7.7 percent) and four (7.7 percent), respectively.
Conclusion Utilisation of the remains of venous catheters in properly-selected patients for short- and medium-term treatment is feasible, cost-effective and safe, and the rates of complications are comparable to cases with conventional catheter insertion.

Keywords: central venous catheter, modified central venous catheter, venous access
Singapore Med J 2009; 50(5): 522-524

Ngoo KS, Rohaizak M, Naqiyah I, Shahrun Niza AS
Correspondence: Prof Rohaizak Muhammad, rohaizak@hotmail.com

ABSTRACT
Introduction Breast cancer is a rare condition among men with a reported incidence of about one percent. Nevertheless, it is thought to behave similarly in both genders. Due to its rarity, male breast cancer is not widely reported, especially in the Asian population.
Methods In a five-year review of our breast cancer surgery series, about 1.6 percent involved male patients. There was a substantial delay in presentation among those men, whose mean age at presentation was 64 years.
Results The majority of patients presented with a painless lump. Histologically, all tumours were ductal in origin and all patients had lower than stage III malignancies. The majority of patients underwent mastectomy and axillary lymph node dissection. All male patients were commenced on adjuvant tamoxifen. The longest survival was 54 months with all patients remaining tumour-free.
Conclusion Malaysian men are at risk of breast cancer and seem to have a better prognosis.

Keywords: breast carcinoma, male breast carcinoma, male breast lump
Singapore Med J 2009; 50(5): 519-521

Ho CCK, Rohaizak M, Zulkifli SZ, Siti-Aishah MA, Nor-Aini U, Sharifah-Noor-Akmal SH
Correspondence: Dr Christopher Ho Chee Kong, chrisckho2002@yahoo.com

ABSTRACT
Introduction This study was conducted to determine the association between serum sex hormone levels and breast cancer.
Methods The study was conducted on newly-diagnosed breast cancer patients who had not received any treatment. Controls were women not known to have any breast disease or hormone-related tumours. Serum hormones were divided into quartiles. Logistic regression adjusting for age and race were done to calculate the odds ratio (OR) and 95 percent confidence interval (CI).
Results A total of 207 subjects were recruited; 73 premenopausal (37 cases, 36 controls) and 134 postmenopausal (68 cases and 66 controls) women. In the premenopausal women, only serum testosterone was positively associated with breast cancer (OR 1.72, 95 percent CI 0.40–7.40), but this was not a significant finding (p-value is 0.468). In the postmenopausal women, oestradiol, progesterone and testosterone were positively associated with breast cancer with a highest to lowest quartile OR of 1.48, 2.35 and 4.23 (95 percent CI 0.59–3.69, 1.11–4.95 and 1.52–11.78, respectively). The OR was significant for both progesterone and testosterone (p-values of 0.025 and 0.006, respectively).
Conclusion There were no statistically significant findings among the premenopausal cases. In postmenopausal women, serum progesterone and testosterone levels were significantly associated positively with the odds of having breast cancer.

Keywords: breast cancer, hormones, postmenopausal cancer risk, progesterone, sex hormones, testosterone
Singapore Med J 2009; 50(5): 513-518

Yadav SPS, Aggarwal N, Julaha M, Goel A
Correspondence: Dr Anuj Goel, dranujgoel@rediffmail.com

ABSTRACT
Introduction To date, myringoplasty conducted under the operating microscope has been found to have its limitations. With the introduction of the endoscope into other branches of surgery, there have been attempts at its utilisation in otology.
Methods Endoscope-assisted myringoplasty was carried out in 50 patients aged 18–45 years using the temporalis fascia graft. The middle ear was examined through perforation in order to exclude cholesteatoma.
Results The overall success rate of the graft uptake and improvement in conductive deafness as air-bone gap closure was achieved in 80 percent of cases.
Conclusion Endoscopic myringoplasty was found to be equally effective, less morbid and very cost-effective in small central perforations. However, it is not applicable in all cases, especially in those with large perforations.

Keywords: conductive deafness, endoscopic myringoplasty, myringoplasty, otoendoscopy, tympanoplasty
Singapore Med J 2009; 50(5): 510-512

Ngo SYA, Ong SHJ, Ponampalam R
Correspondence: Dr Adeline Ngo, gaensy@sgh.com.sg

ABSTRACT
Introduction Stonefish, belonging to the genus Synanceia and classified under the Synanceiidae family, are commonly found in the shallow waters of the Indo-Pacific region and are considered the most dangerous and venomous of this family. The aim of the study was to describe the presenting features, clinical course and current management of this series of patients with stonefish envenomation presenting to a tertiary general hospital in Singapore.
Methods Data involving stonefish stings was retrospectively retrieved from the Singapore General Hospital Accident & Emergency Emerge Version 3.7.6 database from October 2004 to September 2006. Information, such as the patients’ demographics, date and location of the incident, identity of the fish, local or systemic effects, pain score (upon arrival and after treatment), investigations and treatment as well as the outcome of the patients, were evaluated.
Results 30 cases were identified. The median age of the patients was 28 years. The majority of patients were male (80 percent) and 47 percent of cases were foreign nationals. Most incidences occurred on weekends/public holidays(77percent), with November having the highest number of cases (seven cases). The majority of cases (80 percent) arrived at the hospital within two hours of envenomation. Symptoms included extreme pain, swelling and redness of the affected limbs. 24 (80 percent) patients received hot water soak treatment and 27 (90 percent) patients received either intramuscular pethidine or diclofenac for analgesia, where nine patients (33 percent) required additional analgesics after a period of observation. 17 patients (58 percent) were treated and discharged, eight (26 percent) were referred to a specialist for follow-up and five (16 percent) were admitted for an average of three days. 13 out of 25 patients (52 percent) were discharged with antibiotics. One case complained of persistent pain and hyperalgesia five months post-envenomation. One patient required surgical intervention. No deaths and systemic symptoms were reported.
Conclusion Cases of stonefish envenomation that presented to our hospital showed that the majority of patients were young male adults. Stonefish envenomation, though it rarely kills, can cause extreme pain, swelling and erythema, which can be managed with symptomatic treatment.

Keywords: bites, fish venom, poisoning, stings, stonefish envenomation, stonustoxin, Synanceia horrida, Synanceiidae
Singapore Med J 2009; 50(5): 506-509

Chia YC, Yeoh ESH, Ng CJ, Khoo EM, Chua CT
Correspondence: Prof Chia Yook Chin, chiayc@um.edu.my

ABSTRACT
Introduction Calcium channel blockers are well established modalities for the treatment of hypertension. However, in spite of the availability of many efficacious agents, hypertension control continues to be poor. One reason is poor tolerability due to adverse events. Racial differences also exist. Lercanidipine, a third-generation calcium channel blocker, is associated with better tolerability. However, it has not been studied in the Asian population. This study examines its efficacy and tolerability in Asian subjects of different ethnicities.
Methods This was an eight-week open label study of adults with mild to moderate hypertension. Blood pressure (BP), pulse rate, self-administered symptom check and laboratory evaluations were done at baseline. Patients were prescribed 10 mg lercanidipine, with up-titration to 20 mg if BP was not controlled at Week 4. Baseline evaluations were repeated at Week 8. Adverse events were also enumerated.
Results 27 patients (mean age 53.4 +/- 12.1 years) completed the study. The baseline systolic BP (SBP), diastolic BP (DBP) and heart rate was 159 +/- 12.2, 96.6 +/- 7.7 mmHg and 71 +/- 13/min, respectively. Three racial groups were represented. SBP and DBP decreased significantly after four weeks of therapy. A further reduction to 139 +/- 14.3 and 88 +/- 9.8 (p-value is less than 0.0001) was seen in Week 8. The absolute SBP and DBP reduction was 20.5 mmHg (95 percent confidence interval [CI] 16.5–24.5, p-value is less than 0.0001) and 9.3 mmHg (95 percent CI 6.2–12.5, p-value is less than 0.0001), respectively. All adverse symptoms, except for palpitations, were reduced at the end of the study.
Conclusion Lercanidipine is efficacious and well tolerated in Asians of different ethnicities. Its BP lowering effects and tolerability in Asians appear to be similar to other studies on Caucasians and other calcium channel blockers.

Keywords: blood pressure, calcium channel blockers, hypertension, lercanidipine
Singapore Med J 2009; 50(5): 500-505

Yousuf RM, Fauzi ARM, How SH, Akter SFU, Shah A
Correspondence: Dr R M Yousuf, drmyrathor@yahoo.com

ABSTRACT
Introduction Optimal patient care varies considerably from place to place and is influenced by scientific as well as social developments. The purpose of this study was to investigate awareness and pertinent issues regarding informed consent among hospitalised patients and to determine lapses, in order to improve the standard of care.
Methods A questionnaire-based cross-sectional survey was conducted among inpatients at a tertiary care level hospital.
Results 90 percent of patients were aware of their rights, and 85 percent had enough information regarding their illness and modality of treatment. However, treatment options were discussed with 45 percent of cases only, and 65 percent of patients were informed of their duration of treatment. Most of the patients from the surgical group, haemodialysis unit and those with minor ailments were very satisfied with the doctors (92 percent, 86 percent and 96 percent, respectively), as opposed to only 36 percent of cancer patients and 70 percent of acquired immunodeficiency syndrome (AIDS) patients (p-value is less than 0.0001). Almost all patients (99 percent) said that their religious beliefs were respected by the staff and they had no problems in accessing them in times of need. Informed consent was obtained by the doctor in 98 percent of cases and by the nurse in two percent. 98 percent of the patients mentioned that their treatments/examinations were conducted in an atmosphere of privacy and that their personal information was kept confidential by their doctors.
Conclusion Patients were reasonably informed about their illness. Their privacy and religious beliefs were duly respected. Treatment options and the duration of treatment were not discussed with all patients. Cancer and AIDS patients were less satisfied with the attending staff. The results suggest that there is a need for periodic surveys of patient satisfaction with the quality of care.

Keywords: informed consent, patient-centred care, patient confidentiality, patients’ privacy, patients’ rights
Singapore Med J 2009; 50(5): 494-499

Ngow HA, Wan Khairina WMN, Teh LK, Lee WL, Harun R, Ismail R, Salleh MZ
Correspondence: Dr Harris Ngow, harrisngow@gmail.com

ABSTRACT
Introduction Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.
Methods A total of 565 Malay and Chinese subjects, including 191 patients prescribed warfarin, were recruited into the study. The healthy unrelated volunteers were also blood donors and they were confirmed to be physically fit before participating in the study. For the patients group, their medical records were reviewed for the relevant clinical data. 5 ml of blood was taken from each subject, and DNA was isolated and used for identification of the CYP2C9 allele *1, *2, *3 and *4 using nested-allele-specific-multiplex-polymerase chain reaction.
Results CYP2C9*1, *2 and *3 were detected among the healthy unrelated individuals but only CYP2C9 *1 and *3 were found in the diseased patients. Among the healthy Malays, 92.8 percent had CYP2C9*1/*1, 2.6 percent had CYP2C9*1/*2 and 4.6 percent had CYP2C9*1/*3 genotypes. Among the Chinese, 92.3 percent had CYP2C9*1/*1 and 7.7 percent had CYP2C9*1/*3, but CYP2C9*2 and *4 were not found in the Chinese. Among the warfarin-treated group, only CYP2C9*1 and *3 were detected. Even though some alleles were not detected among the patients, suggesting the possible role of CYP2C9 in certain disorders, the sample size of the current study is too small to be able to arrive at any conclusive results.
Conclusion Based on the above-observed genotypes, the prevalence of CYP2C9*2 and *3 was low in healthy and warfarin-treated Malays and Chinese in Malaysia. Further studies are required to support the clinical effectiveness of pharmacogenomics testing.

Keywords: CYP2C9 frequency, genetic polymorphism, pharmacogenomics testing, warfarin
Singapore Med J 2009; 50(5): 490-493