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Fulltext Revision surgery for developmental dysplasia of the hip

Chidambaram S, Abd Halim AR, Yeap JK, Ibrahim S

Med J Malaysia, 2005 Jul;60 Suppl C:91-8.
PMID: 16381291

Revision surgery following failed open reduction for developmental dysplasia of the hip (DDH) is technically demanding. We reviewed 12 patients in our institution that required a revision surgery between January 1994 and December 2003. The aims of this study are to identify the causes of redislocation after the primary open reduction and to determine the clinical and radiological outcome after the revision surgery. The mean age at presentation for DDH was 31 months (range 1-84) and the mean age at primary open reduction surgery was 38 months (range 15-84) and the mean age at revision surgery was 69 months (range 21-180). The mean follow-up period after revision surgery was 20 months (range 3-84). All the revision surgery was performed via an anterior Smith Peterson approach. The most common cause for redislocation was inadequate exposure and failure to release the obstructing soft tissues around the hip. The bony factors for redislocation included failure to perform a femoral shortening and excessive derotation of an anteverted femoral head combined with a Salter osteotomy. Three cases with posterior acetabular wall deficiency needed immobilization of the hip in extension as the hip tended to dislocate in flexion. Six patients had limb length discrepancy ranging from 1 cm to 4 cm and 50% developed avascular necrosis. Only 2 patients were asymptomatic and the majority had a limp and limitation of motion. All were pain free except one. In view of the technically demanding surgery and poor results after revision, the surgeon should recognize the pathology and ensure that the primary procedure achieves a stable and concentric reduction.
Fulltext Modular endoprosthetic replacement after total femur resection for malignant bone tumor

Faisham WI, Zulmi W, Halim AS

Med J Malaysia, 2005 Jul;60 Suppl C:45-8.
PMID: 16381283

Total femur endoprothesis is an alternative replacement for massive malignant bone tumor with intramedullary extension or skip lesion. Four patients underwent total femoral resection and replacement with megaprosthesis: three had primary malignant bone tumor and one had salvage procedure for aseptic loosening of the distal femoral replacement. Tumor-free margins were achieved in all patients with two patients required vascularized latissimus dorsi free flap cover for reconstruction of soft tissue defects. The average follow-up was 24 months (range 16 - 60 months). All four patients were still alive with three of them being disease-free and one survived even with the presence of lung metastasis. The functional results obtained were either excellent or good in all patients in accordance to the Musculoskeletal Tumors Society grading system.
Fulltext Slipped capital femoral epiphysis (SCFE): a 12-year review

Kamarulzaman MA, Abdul Halim AR, Ibrahim S

Med J Malaysia, 2006 Feb;61 Suppl A:71-8.
PMID: 17042235

Slipped capital femoral epiphysis (SCFE) is a relatively uncommon hip disorder in adolescents and its prevalence in Malaysia has not been studied. This retrospective study is undertaken to provide an overview of a 12-year review of SCFE treated in our institution. Fourteen patients (19 hips) with slipped capital femoral epiphysis (SCFE) admitted to Hospital UKM from 1990 to 2002 were reviewed with respect to demographic profile, functional outcome according to the Iowa Hip Score, and complications. There were ten boys (average age, 12.5 years) and four girls (average age, 12 years). Eight were Malays and six were Indians. The average body mass index was 26.1 verweight). The left hips (11 hips) were affected more than the right hips (eight hips). Five patients had bilateral slips. Thirteen hips were considered stable while the other six hips were unstable. The majority of cases were moderate slips (12 hips), four hips had severe slips while three hips had mild slips. Several methods of treatment were instituted. These include in situ cannulated screw fixation (11 hips), Knowles pin fixation (three hips) and gentle closed manipulative reduction with cannulated screw fixation (three hips). One patient with bilateral slips refused surgical treatment. Based on the Iowa Hip Score, most patients (nine) had satisfactory results (excellent or good), three had fair results while one patient had a poor result. Avascular necrosis developed in five hips while chondrolysis occurred in one hip. In situ cannulated screw fixation is the treatment of choice. SCFE is an uncommon condition in Malaysia.
Fulltext Versatility of the latissimus dorsi flap in upper limb salvage tumour surgery

Dorai AA, Halim AS, Zulmi W

Med J Malaysia, 2004 Dec;59 Suppl F:42-6.
PMID: 15941160

Reconstructive surgeons often encounter complex soft tissue and skeletal defects following oncological surgery. Soft tissue defects after wide resection in upper extremities posses a difficult challenge to find adequate tissue for reconstructing these defects. Paucity of local tissues dictates the requirement of loco-regional or distant flaps for these complex soft tissue defects which often exposes tendons, bones, nerves and joints. The latissimus dorsi muscle is a near ideal flap for the reconstruction because of the long neurovascular pedicle, ease of mobilization and its expendability. It can be rotated, with or without overlying skin, to cover soft tissue defects of the shoulder arm and elbow. Due to the large size of the muscle, it can be used to resurface the soft tissue defects and cover all major structures. Eleven consecutive cases were reviewed in which latissimus dorsi myocutaneous flap was used to reconstruct soft tissue defects of the upper limb following radical tumor resection. Flap survival was 100% with nominal donor site morbidity.
Reconstructive treatment following resection of high-grade soft-tissue sarcomas of the lower limb

Leow AM, Halim AS, Wan Z

J Orthop Surg (Hong Kong), 2005 Apr;13(1):58-63.
PMID: 15872402

To review the role of free tissue transfer in reconstructive surgery following resection of high-grade soft-tissue sarcomas of the lower limb.
A prospective study of the acceptability of Today vaginal contraceptive sponge among Malaysian women

Ismail MT, Halim AJ, Arshat H

Malays J Reprod Health, 1987 Jun;5(1):17-21.
PMID: 12269177
Filshie clip sterilization -- single puncture laparoscopic approach (a preliminary report)

Ismail MT, Arshat H, Halim AJ

Malays J Reprod Health, 1988 Dec;6(2):90-6.
PMID: 12342172

PIP: In 1986, single puncture laparoscopic application of the Filshie clip was introduced into Malaysia's National Population and Family Development Board's female sterilization program for an evaluation. A total of 42 female sterilizations were performed by this method between June 1986 and December 1986. Laparoscopy was performed on an outpatient basis under local anesthesia. In 37 cases, the sterilization was interval. Filshie clips were successfully applied to the fallopian tubes of 40 women; in the remaining 2 cases, the latching mechanism jammed and Falope rings were used instead. The average time from application of 1st clip to skin closure was 10 minutes. During clip application, technical problems (faulty applicator, clip fell into the pelvic cavity, failure of latching mechanism) were encountered in 4 cases and surgical difficulties (poor visualization, hydrosalpinx, and tubal adhesions) occurred in 10 cases. In general, complications were minimal: 1 patient developed cynosis after anesyhesia (Pethidine) injection, the omentum was torn during introduction of the trocar in another, and a 3rd patient developed thrombophlebitis at the intravenous site. Only 1 pregnancy was recorded during the follow-up period; this occurred 15 months postoperatively and was intrauterine. Given the facts that this procedure is easy to learn, fast and simple, associated with no more complications than other laparoscopic procedures, and is cosmetically more acceptable to women, its more widespread application is recommended.
Persistent hypertension in lupus nephritis and the associated risk factors

Shaharir SS, Mustafar R, Mohd R, Mohd Said MS, Gafor HA

Clin Rheumatol, 2015 Jan;34(1):93-7.
PMID: 25373448 DOI: 10.1007/s10067-014-2802-0

Arterial hypertension (HPT) burden up to two third of systemic lupus erythematosus (SLE) patients and contributes to accelerated atherosclerosis and cardiovascular (CV) risk. We aim to determine the prevalence of HPT among lupus nephritis (LN) patients who were in complete remission (CR) for a minimum of 6 months, with estimated glomerular filtration rate (eGFR) of >60 mL/min/1.73 m(2). This is a cross-sectional study of 64 LN patients who attended Nephrology/SLE Clinic at The National University of Malaysia Medical Centre (UKMMC). Persistent hypertension (blood pressure (BP) ≥140/90 mmHg for at least two occasions), CR for a minimum of 6 months and eGFR of >60 mL/min/1.73 m(2) were identified. Univariate and multivariate analyses were performed to determine the demographic and disease characteristics associated with HPT. Thirty-four of them (53.1 %) were hypertensive. Persistent HPT was associated with disease duration, acute kidney injury and high BP at the onset of LN, longer duration interval to achieve CR, number of relapses and cyclosporine A (CyA) use. There were no associations between histological classes, nephrotic range proteinuria, body mass index and waist circumference with HPT. Factors independently associated with HPT were disease duration OR 1.06 [95 %CI (0.91-1.24)], longer duration interval to achieve CR OR 1.104 [95 %CI (1.02-1.19)], number of relapses OR 2.53 [95 % CI (1.01-6.3)] and CyA use OR 5.3 [95 % CI (1.14-23.9)]. The prevalence of HPT among LN is high despite in remission. Aggressive treatment is important to achieve early CR and to prevent relapses.
Study site: Nephrology/SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext Systemic lupus erythematosus with a non functioning pituitary macroadenoma

Nadira U, Cader RA, Kong NC, Mohd R, Gafor HA

Am J Case Rep, 2012;13:160-2.
PMID: 23569517 DOI: 10.12659/AJCR.883248

BACKGROUND: Malignancies are more common in patients with systemic lupus erythematosus (SLE) than the general population. SLE patients are recognized to have higher prolactin levels. However, there are very few reported cases of SLE with pituitary adenomas.
CASE REPORT: We report the second case of a pituitary adenoma in a patient with underlying SLE. A 51 year old lady presented with blurred vision and magnetic resonance imaging of the brain demonstrated a pituitary macroadenoma with mildly elevated serum prolactin levels. The diagnosis of a non functioning pituitary macroadenoma was confirmed histologically. The diagnosis of SLE was made on the basis of thrombocytopenia, antinuclear antibodies, anti double stranded DNA antibodies and lupus nephritis (confirmed on renal biopsy). The patient initially received medical therapy with carbegoline, followed by transsphenoidal neurosurgery for the pituitary macroadenoma. SLE with lupus nephritis was treated with steroids and low dose intravenous cyclophosphamide.
CONCLUSIONS: Hyperprolactinaemia is prevalent in twenty to thirty percent of SLE patients but it is rarely due to a prolactinoma. The source of excessive circulating prolactin in SLE patients has not been fully determined.
KEYWORDS: pituitary macroadenoma; prolactin; systemic lupus erythematosus
Fulltext Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE

Br J Clin Pharmacol, 2015 Nov;80(5):1064-75.
PMID: 25959850 DOI: 10.1111/bcp.12678

AIMS: The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis.
METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events.
RESULTS: Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023).
CONCLUSIONS: This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.
KEYWORDS: lupus nephritis; mycophenolic acid; pharmacodynamics; pharmacokinetics; prednisolone; treatment outcome
Study site: Nephrology and SLE Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Development of improved dosing regimens for mycophenolate mofetil based on population pharmacokinetic analyses in adults with lupus nephritis

Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE

Eur J Drug Metab Pharmacokinet, 2017 Dec;42(6):993-1004.
PMID: 28536776 DOI: 10.1007/s13318-017-0420-3

BACKGROUND AND OBJECTIVE: Mycophenolic acid (MPA) provides effective treatment for lupus nephritis patients. Owing to its large pharmacokinetic variability, it is questionable whether standard fixed dose therapy can achieve optimal MPA exposure. The aim of this study was to develop a population pharmacokinetic model of MPA and its metabolite, 7-O-MPA-β-glucuronide (MPAG), to identify important covariate influences and better predict patient dosing requirements.
METHODS: MPA and MPAG concentration-time profiles were collected from 25 patients receiving mycophenolate mofetil (MMF) with or without cyclosporine (CsA) co-therapy. Samples were collected pre-dose and at 1, 2, 4, 6 and 8 h post-dose on one or two occasions.
RESULTS: A total of 225 and 226 concentration-time measurements of MPA and MPAG, respectively, were used to develop the model, utilizing NONMEM® software. A two-compartment model with first-order absorption and elimination for MPA and a one-compartment model with first-order elimination and enterohepatic circulation (EHC) for MPAG best described the data. Apparent clearance of MPAG (CL/F MPAG) significantly decreased with reducing renal function and extent of EHC was reduced with concomitant CsA use. Simulations using the final model showed that a 70-kg subject with a creatinine clearance of 90 mL/min receiving concomitant CsA would require 1.25 g of MMF twice daily while a similar subject who did not receive concomitant CsA would require 0.75 g twice daily to achieve a MPA area under the concentration-time curve from 0 to 12 h (AUC0-12) of 45 mg·h/L.
CONCLUSION: A 'tiered' dosing approach considering patient renal function and CsA co-therapy, rather than a 'one dose fits all' approach, would help individualize MMF therapy in adult lupus nephritis patients to ensure more patients have optimal MPA exposure.
Study site: Nephrology and Systemic Lupus Erythematosus (SLE) Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext Angiotensin-converting enzyme gene polymophism in adult primary focal segmental glomerulosclerosis

Mohd R, Wahab ZA, Cader R, Gafor HA, Radzi AM, Shah SA, et al.

J Clin Med Res, 2014 Aug;6(4):245-51.
PMID: 24883149 DOI: 10.14740/jocmr1550w

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) accounts for a third of biopsy-proven primary glomerulonephritis in Malaysia. Pediatric studies have found the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to be associated with renal disease progression. The aim of this study was to determine the prevalence of the ACE (I/D) genotypes in adult primary FSGS and its association with renal outcome on follow-up.
METHODS: Prospective observational study involving primary FSGS patients was conducted. Biochemical and urine tests at the time of study were compared to the time of the diagnosis and disease progression analyzed. ACE gene polymorphism was identified using polymerase chain reaction amplification technique and categorized into II, ID and DD genotypes.
RESULTS: Forty-five patients with a median follow-up of 3.8 years (interquartile range: 1.8 - 5.6) were recruited. The commonest genotype was II (n = 23, 51.1%) followed by ID (n = 19, 42.2%) and DD (n = 3, 6.7%). The baseline characteristics were comparable between the II and non-II groups at diagnosis and at study recruitment except that the median urine protein-creatinine index was significantly lower in the II group compared to the non-II group (0.02 vs. 0.04 g/mmol (P = 0.03). Regardless of genotypes, all parameters of renal outcome improved after treatment.
CONCLUSION: The II followed by ID genotypes were the predominant ACE gene alleles in our FSGS. Although the D allele has been reported to have a negative impact on renal outcome, treatment appeared to be more important than genotype in preserving renal function in this cohort.
Report of a rare case of carcinosarcoma of the maxillary sinus with sternal metastasis

Cheong JP, Rahayu S, Halim A, Khir A, Noorafidah D

Ear Nose Throat J, 2014 Jun;93(6):E1-4.
PMID: 24932822

Carcinosarcoma is a highly aggressive and infiltrative tumor. A finding of this tumor in a paranasal sinus is exceedingly rare. We describe the case of a 61-year-old man who presented with a mass on the left side of his face. The mass was excised via a total maxillectomy with a modified radical neck dissection. Histologic analysis identified a mixture of carcinomatous and sarcomatous components. Within 1 month of surgery, the patient developed a sternal metastasis, and he died within a short period of time. The aggressive nature of this tumor and its metastases demand early diagnosis and prompt treatment.
Dried irradiated human amniotic membrane as a biological dressing for facial burns--a 7-year case series

Bujang-Safawi E, Halim AS, Khoo TL, Dorai AA

Burns, 2010 Sep;36(6):876-82.
PMID: 20236771 DOI: 10.1016/j.burns.2009.07.001

Facial burns are common and have a significant impact on patient function and psychosocial well being. Human amnion has been used for many years as a temporary biological wound dressing in the management of partial thickness burns. The observed advantages of human amnion treatment include pain relief, ease of use, prevention of infection and acceleration of wound healing.
The application of glycerol-preserved skin allograft in the treatment of burn injuries: an analysis based on indications

Khoo TL, Halim AS, Saad AZ, Dorai AA

Burns, 2010 Sep;36(6):897-904.
PMID: 20299154 DOI: 10.1016/j.burns.2009.03.007

Glycerol-preserved skin allograft (GPA) plays a crucial role in the management of burns. Its indications include wound-bed preparation, definitive dressing and sandwich grafting technique.
In vitro biocompatibility of chitosan porous skin regenerating templates (PSRTs) using primary human skin keratinocytes

Lim CK, Yaacob NS, Ismail Z, Halim AS

Toxicol In Vitro, 2010 Apr;24(3):721-7.
PMID: 20079826 DOI: 10.1016/j.tiv.2010.01.006

Biopolymer chitosan (beta-1,4-d-glucosamine) comprises the copolymer mixture of N-acetylglucosamine and glucosamine. The natural biocompatibility and biodegradability of chitosan have recently highlighted its potential use for applications in wound management. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability, but it is unknown as to what degree. Hence, the biocompatibility of the chitosan porous skin regenerating templates (PSRT 82, 87 and 108) was determined using an in vitro toxicology model at the cellular and molecular level on primary normal human epidermal keratinocytes (pNHEK). Cytocompatibility was accessed by using a 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assay from 24 to 72h. To assess the genotoxicity of the PSRTs, DNA damage to the pNHEK was evaluated by using the Comet assay following direct contact with the various PSRTs. Furthermore, the skin pro-inflammatory cytokines TNF-alpha and IL-8 were examined to evaluate the tendency of the PSRTs to provoke inflammatory responses. All PSRTs were found to be cytocompatible, but only PSRT 108 was capable of stimulating cell proliferation. While all of the PSRTs showed some DNA damage, PSRT 108 showed the least DNA damage followed by PSRT 87 and 82. PSRT 87 and 82 induced a higher secretion of TNF-alpha and IL-8 in the pNHEK cultures than did PSRT 108. Hence, based on our experiments, PSRT 108 is the most biocompatible wound dressing of the three tested.
The effect of vitamin E on basic fibroblast growth factor level in human fibroblast cell culture

Rashid SA, Halim AS, Muhammad NA

Med J Malaysia, 2008 Jul;63 Suppl A:69-70.
PMID: 19024988

Basic fibroblast growth factor (bFGF) is angiogenic and effective in down-regulating excess collagen production. The aim of this study is to evaluate the effectiveness of vitamin E (Tocotrienol Rich Fraction) in altering the level of bFGF, a cytokine involved in the scar formation process. In this model, normal human fibroblasts were treated with various concentrations of vitamin E at different time frames. The levels of bFGF were determined by Enzyme-Linked Immunosorbant Assay (ELISA). This study demonstrated that Tocotrienol Rich Fraction (TRF) stimulated bFGF production by fibroblast and postulate that vitamin E may decrease aberrant scar formation.
Fulltext Surgical management of a massive facial hemangioma

Baharudin A, Samsudin AR, Halim AS, Shafie MA

Med J Malaysia, 2007 Aug;62(3):254-5.
PMID: 18246921 MyJurnal

Hemangiomas are the most common congenital lesions in man and occur predominantly in the head and neck region. Massive hemangioma especially near vital organs or structures pose a challenge to surgeons. With the availability of expertise in embolization of feeding vessel of the hemangioma and reconstructive techniques we were able to manage successfully a complicated case of massive facial hemangioma.
Use of dermal regeneration template (INTEGRA) in reconstructive burn surgery

Sasidaran R, Dorai AA, Sulaiman WA, Halim AS

Med J Malaysia, 2008 Jul;63 Suppl A:29.
PMID: 19024967

We present our two year experience with a dermal regeneration template (INTEGRA) in burn reconstructive surgery for contracture release as well as a reconstructive tool for management of soft tissue loss.
Fulltext An extensive sinonasal osteosarcoma mimicking chondrosarcoma

Shahid H, Baharudin A, Halim AS, Biswal BM, Jihan WS

Med J Malaysia, 2007 Jun;62(2):171-2.
PMID: 18705458 MyJurnal

Osteosarcoma is a rare tumour in the sinonasal region. Early diagnosis is essential for adequate management and better prognosis and this requires a meticulous histopathological examination. Reported is a case of osteosarcoma misdiagnosed as chondrosarcoma and treated by surgery followed by radiotherapy. However, appropriate diagnosis and pre-operative chemotherapy would have been significant in the prognosis. The pitfall of accurate diagnosis and the subsequent treatment is discussed in order to find the ways to maximize five years survival which is not more than 25% in this type of lesions.

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