VACTERL association is a rare genetic disorder involving at least three of the following congenital
malformations: vertebral defects (V), anal atresia (A), cardiac defects (C), trachea-oesophageal fistula with
or without oesophageal atresia (TE), renal anomalies (R) and limb abnormalities (L). Until now, the
aetiology of VACTERL association is unknown, particularly at the molecular level. Here, we performed
whole exome sequencing (WES) of an infant with VACTERL association. The patient was delivered
prematurely at 30 weeks and had 4/6 of the VACTERL malformations. Trio-WES analysis was performed
using Torrent Suite and ANNOVAR. Polymorphisms with an allele frequency of >0.01 were excluded, and
the remaining variants were filtered based on de novo mutations, autosomal recessive, X-linked and di-genic
inheritance traits. In this patient, no homozygous, compound heterozygous or X-linked mutations was
associated with VACTERL. However, we identified two heterozygous mutations; KIF27
(ENST00000297814: c.3004A> C:p.N1002H) and GNAS (ENST00000371098: c.205C>A:p.H69N) genes that
were inherited from her father and mother respectively. A de novo, IFT140 gene mutation
(ENST00000426508: c.683C>G:p.S228C) was also identified in this patient. The VACTERL phenotype in
this patient may due to heterozygous mutations affecting KIF27 and GNAS genes, inherited via autosomal
recessive trait. In addition, the IFT140 gene mutation may also be involved. These genes are known to be
directly or non-directly involved in the sonic hedgehog signalling that is known to be implicated in
VACTERL. This is the first report of these genetic mutations in association with VACTERL.
Amenorrhea is a common menstrual problem seen in adolescents. Amenorrhea has been shown to have a negative impact on adolescents' quality of life. In this paper we discuss the various causes and investigations of amenorrhea in adolescents and address management dilemmas for specific conditions. Specific approaches in dealing with adolescents using the HEADSS (Home, Education, Activity, Drugs, Sexual activity, Suicidal) approach are discussed.
Burkholderia pseudomallei infection of the central nervous system (CNS) is rare with less than 50 cases reported over the last 30 years. The retrospective melioidosis study at University Malaya Medical Centre has documented three cases of CNS melioidosis out of more than 160 cases of melioidosis since 1978. There were two patients with brain abscess and one with spinal epidural abscess. The predisposing factors were: one patient was an aboriginal farmer and the other two were diabetic. Their age ranged from 17 to 45 years. Prominent neurological features were limb weakness, cranial nerve palsy (6th and 7th) and visual disturbance. CT brain scan and MRI spine showed abscess formation, subdural collection, and spinal epidural collection, osteomyelitis of vertebra and occipital bone and also sagital sinus thrombosis. All these patients underwent surgical drainage leading to bacteriological diagnosis as well as appropriate long-term antibiotic therapy. All had good recovery at 6 months after completion of treatment.
The aim of this study was to identify risk factors associated with osteoporosis in urban midlife Malaysian women and to assess the effectiveness of lifestyle intervention in bone loss prevention with hormone replacement therapy (HRT) as a positive control. A total of 514 disease-free, uterus-intact, non-HRT-using women aged 45 years and older were recruited into the study. After initial bone mineral density (BMD) assessments, they were randomized into three groups: GI (control), G2 (lifestyle intervention), and G3 (lifestyle intervention with HRT). The study group was composed of 67.5% Chinese, 27.8% Malay, and 4.2% Indians with a mean age of 51.07+/-5.28 years. Two-fifths were postmenopausal, and the prevalence of osteoporosis was 24.1%, seen predominantly at the hip. Postmenopausal women had significantly lower mean BMD and a higher incidence of osteoporosis compared with the premenopausal women, 42.1% vs. 11.1% (p<0.0005). A lower incidence of osteoporosis was found in women who took calcium supplementation regularly as opposed to those who do not, 18.7% vs. 29.3% (p=0.036). Age and a greater postmenopausal duration showed a significant negative association with BMD, whereas higher family income, weight, body mass index, and waist and hip circumference were positively correlated. After 18-20 months, the effect of intervention was assessed based on BMD values of 279 women at baseline and after intervention. Lifestyle intervention alone was effective in premenopausal women, preventing over 90% of spinal bone loss compared with the controls, who lost 11.6% (0.046 g/cm2) bone mass with similar losses of hip bone, 2.0% (0.026 g/cm2) vs. 1.5% (0.020 g/cm2). Premenopausal women on HRT also showed a substantial decrease in spine and hip BMD, 18.6% (0.081 g/cm2) and 9.0% (0.122 g/cm2), respectively. The lifestyle intervention program retarded postmenopausal bone loss by 21% and 37% compared with controls, who lost 9.6% (0.141 g/cm2) and 6.0% (0.138 g/cm2) bone mass at the spine and hip. In comparison, lifestyle intervention with HRT increased postmenopausal BMD by 12.7% (0.216 g/cm2) at the spine and 1.9% (0.042 g/cm2) at the hip. The changes in hip BMD were influenced by current age, ethnicity, and income, while intervention had the strongest effect on spine BMD changes. In conclusion, lifestyle intervention prevented spinal bone loss in premenopausal women and retarded postmenopausal spine and hip bone loss compared with controls. The benefits of physical activity on spine and hip BMD highlight its potential as a safe and cost-effective alternative to HRT, which is not advocated because of its potential adverse effects.
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.