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1.  Self-perception and quality of life among overweight and obese rural housewives in Kelantan, Malaysia 
Obesity, in the past was perceived to be the problem of the rich, but recent studies have reported that the problem of obesity is a worldwide problem and rural population is no less affected. Self-perceived health and weight appropriateness is an important component of weight-loss and eating behaviors and may be mediated by local, social and cultural patterning. In addition to the quality of life assessment, it should therefore be an important focal point for the design and implementation of clinical and public health policies.
The present study was carried out to assess the self-perception of weight appropriateness as well as the quality of life of overweight and obese individual among the rural population particularly among housewives. A total of 421 respondents participated in the study which consisted of 36.6% in the overweight and 63.4% in the obese categories.
the analysis of the survey revealed that self-perception regarding obesity among respondents show common similarities, particularly in self reporting on health, dietary habit and also the concept of beauty and a beautiful body. Character and behavior are highly regarded in evaluating a person’s self-worth in society. The results on the quality of life using the ORWELL 97 instrument show that the quality of life of respondents was moderate. Most of the respondents were aware of their body weight and indicated an intention to lose weight but also reported themselves as healthy or very healthy.
The results of the survey indicated that perception on obesity did not differed very much between respondents, in fact there existed a lot of similarities in their perception about health, quality of life, personal health and self-satisfaction with own body. However, their quality of life was within the normal or moderate level based on the ORWELL 97 assessment. Even though most of the respondents were aware of their body weight and indicated an intention to lose weight they also reported themselves as healthy or very healthy, suggesting that public health messages intended for rural housewives need to be more tailored to health-related consequences of fatness.
PMCID: PMC4328071
Overweight; Obesity; Quality of life; Self-perception; Rural housewives
2.  The Frequency of Anti-Aquaporin-4 Ig G Antibody in Neuromyelitis Optica and Its Spectrum Disorders at a Single Tertiary Referral Center in Malaysia 
Background. In the past the occurrence of neuromyelitis optica in Malaysia was thought to be uncommon and the frequency of anti-aquaporin-4 Ig G antibody was unknown. Objective. To evaluate the frequency of anti-aquaporin-4 Ig G antibody (Anti-AQP4 antibody) amongst patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) and the differences between the seropositive and seronegative groups. Methods. Retrospectively, 96 patients with NMO/high risk syndromes for NMOSD (HRS-NMOSD) were identified out of 266 patients with idiopathic inflammatory demyelinating disease from a single center hospital based registry. Anti-AQP4 seropositivity was found in 38/48 (79.2%) with NMO, 12/21 (57.1%) with brain involvement at high risk for NMOSD, 12/15 (80%) with transverse myelitis (i.e., 11/15 with relapsing transverse myelitis and one with monophasic transverse myelitis), and 3/7 (42.8%) with relapsing optic neuritis. Sixty-five out of 96 patients, that is, 67.7%, with NMO/HRS for NMOSD were seropositive. Seropositivity was significantly associated with female gender, a higher number of mean relapses, that is, 5.15 ± 4.42 versus 2.10 ± 1.68, longer length of spinal cord lesions, that is, 6.6 ± 4.9 versus 2.9 ± 2.5, vertebral bodies, higher EDSS, 4.5 ± 2.4 versus 2.4 ± 2.6, presence of paroxysmal tonic spasms, and blindness (unilateral/bilateral); P < 0.001. Longitudinally extensive cord lesions (contiguous or linear), presence of lesions in the cervical and thoracic regions, and involvement of the central gray matter or holocord regions on axial scans, were also significantly associated with seropositivity; P < 0.001. Conclusion. NMO and HRS for NMOSD are present in larger numbers than previously thought in Malaysia. More than 2/3rds are seropositive. Seropositive and seronegative NMO/NMOSD have differences that are useful in clinical practice.
PMCID: PMC4274866  PMID: 25548676
3.  Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients 
Molecular Cancer  2014;13:142.
MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types.
We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n = 150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed.
The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n = 11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n = 90, Median 0.09; IQR 0.04-0.29) (p = 0.028). In the subgroup of patients without synchronous metastases (n = 90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 1.16, p = 0.021 and HR 1.20, p = 0.015 respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable (HR1.30, p < 0.001, and HR 1.31, p = 0.003 respectively for 0.10 unitary increase of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p = 0.009) for OS and from 0.735 to 0.767 (p = 0.050) for DFS.
Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.
PMCID: PMC4055397  PMID: 24897960
Breast cancer; microRNA; Metastasis; RT-qPCR
4.  Association between household food insecurity and nutritional outcomes among children in Northeastern of Peninsular Malaysia 
Nutrition Research and Practice  2014;8(3):304-311.
The purpose of the study was to investigate the relationship between household food insecurity and nutritional status of children in low-income households. A cross sectional study involved a survey of households (n = 223) receiving the financial assistance.
Eligible mothers that fulfilled the inclusion criteria such as non-pregnant, non-lactating mothers, aged 18 to 55 years with their youngest children aged 2 to 12 years, were purposively selected. The Radimer/Cornell hunger and food-insecurity instrument was administered and children's height and weight were measured.
About 16.1% of the households were food secure, while 83.9% experienced some kind of food insecurity. Out of food insecure category, 29.6% households were food insecure, 19.3% women were individual food insecure and 35.0% fell into the child hunger category. Education of the mother (P = 0.047), household size (P = 0.024), number of children (P = 0.024), number of children going to school (P = 0.048), total monthly income (P < 0.001), income per capital (P < 0.001), number of household members contributing to the income (P = 0.018) and food expenditure (P = 0.006) were significant risk factors for household food insecurity. The prevalence of underweight, stunting and wasting in children were 61.0%, 61.4% and 30.6% respectively. Based on multinomial logistic regression, children in food-insecure households were 2.15 times more likely to be underweight and three times to be stunted than children in the food-secure households.
The findings suggest that household food insecurity is associated with the nutritional status of the children in the rural area of Northeastern Peninsular Malaysia.
PMCID: PMC4058565  PMID: 24944776
Northeastern Peninsular Malaysia; child hunger; household food insecurity; nutritional status
5.  Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics 
Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.
PMCID: PMC3888747  PMID: 24455266
6.  Tumor associated macrophages polarization dictates the efficacy of BCG instillation in non-muscle invasive urothelial bladder cancer 
To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy.
Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence. Correlations between immunofluorescence measured Mtot, M1 and M2 infiltration and clinicopathological parameters were evaluated using Spearman and Mann–Whitney methods. The recurrence-free survival rate was calculated using the Kaplan-Meier method.
CD68 positive cells (Mtot) were observed in all specimens tested. High Mtot, M1 and M2 infiltration was observed in patients with disease recurrence, even before endovescical BCG instillation. Significant value for M2 infiltration (p = 0,042) was found calculating significativity between two group medians before BCG therapy. p = 0,072 and p = 0,180 were observed correlating median of Mtot and M1 between two groups of patients respectively. Values of p = 0,44, p = 0,23 and p = 0,64 from correlation between DFS and Mtot, M1 and M2 median in patients before endovescical BCG instillation, were calculated respectively. Comparing DFS and Mtot, M1 and M2 median in patients group after endovescical BCG instillation significant values were obtained (p = 0,020; p = 0,02; and p = 0,029 respectively).
M2 tumor infiltration could be a prognostic value of recurrence in patients with NMIBC.
PMCID: PMC4029537  PMID: 24423367
Bladder cancer; Endovescical instillation; Tumor-associated macrophages; Macrophages polarization; Prognosis
7.  The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients 
Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio-naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count. The median value of the two macrophage populations density and the median value of M1/M2 ratio were used as cut-off. Twenty-seven patients with M1 density above-the-median had a significantly higher survival compared to those below the median. Twenty-six patients with M1/M2 ratio above the median showed median OS of 27.2 months compared to 15.5 months of the patients below the median. No association between M2 macrophage density and patient's outcome was found. In multivariate analysis, M1/M2 was a positive independent predictor of survival. The M1 macrophage density and M1/M2 ratio, as confirmed in multivariate analysis, are factors that can help in predicting patients survival time after radical surgery for gastric cancer.
PMCID: PMC4117554  PMID: 24283947
tumour associated macrophages; M1 polarization; M2 polarization; prognostic factor; gastric cancer
8.  Necrotizing Fasciitis on the Right Side of the Neck with Internal Jugular Vein Thrombophlebitis and Septic Emboli: A Case of Lemierre’s-Like Syndrome 
Lemierre’s syndrome (LS) is a rare life-threatening infective condition typically starting with an oropharyngeal infection causing thrombophlebitis and metastatic abscesses. The most common aetiology of LS is Fusobacterium necrophorum; however, it can also occur after infection with other organisms. LS mainly affects young healthy adults. The initial infection site can be in the head and neck or in the abdomen. The morbidity rate of this disease is high despite aggressive treatments. In this article, we report a 63-year-old male patient with uncontrolled diabetes mellitus, presenting with Klebsiella pneumoniae infection-induced necrotizing fasciitis on the right side of the neck, leading to LS.
PMCID: PMC3957351  PMID: 24643401
necrotizing fasciitis; Lemierre syndrome; Fusobacterium necrophorum; Klebsiella pneumoniae
9.  Mesenchymal Chondrosarcoma: A Case Report 
Mesenchymal chondrosarcoma is a rare disease with poor prognosis. Treatment including wide or radical excision is very important. Radiotherapy and chemotherapy are additional treatment options, but no conclusive results for their efficacy have been shown until date. Imaging modalities can give important clues for diagnosis and management planning. Angioembolization before surgery could be useful as prophylaxis to control intraoperative bleeding, increasing the likelihood of complete resection.
PMCID: PMC3743986  PMID: 23966829
mesenchymal chondrosarcoma; extraskeletal; therapeutic embolization
10.  Image-guided chemoport insertion by interventional radiologists: A single-center experience on periprocedural complications 
To report our early experience in image-guided chemoport insertions by interventional radiologists.
Materials and Methods:
This was a cross-sectional study conducted in a tertiary center with 161 chemoport insertions done from June 2008 to June 2010. The chemoports were inserted either at the angiography suite or at the mobile operation theater unit. Ninety percent of the chemoports had right internal jugular vein (IJV) as the entry site. Other entry sites included the left IJV, subclavian veins and the inferior vena cava. Immediate and early complications were recorded. All insertions were performed under image guidance with the aid of ultrasound and fluoroscopy.
The technical success rate was 99.4%. In terms of immediate complications, there were only two cases of arterial puncture that resolved with local compression. No pneumothorax or air embolism was documented. Twenty-six early complications were recorded. The most common early complication was catheter blockage (12/161; 7.4%), followed by catheter-related infection (9/161; 5.6%). Other complications were catheter malposition, venous thrombosis and catheter dislodgement or leak. A total of 11 (6.8%) chemoports had to be removed within 30 days; most of them were due to infections that failed to respond to systemic antibiotic therapy. In terms of place of procedure, there were no significant differences in complication rates between the angiography suite and the mobile operation theater unit.
Image-guided chemoport insertion by interventional radiologist gives low periprocedural complication rates. Using right IJV as the entry site, the image guidance gives good success rate with least complication.
PMCID: PMC3777320  PMID: 24082475
Central venous catheterization; complications; interventional radiology; vascular access ports
11.  Percutaneous Catheter-Based Rheolytic Thrombectomy for Massive Pulmonary Embolism: A Case Report 
Pulmonary thromboembolism is a life-threatening cardiovascular condition. The mortality rate is high in its current management. Besides supportive treatments, systemic thrombolysis and surgical thrombectomy play important roles in the comprehensive management of pulmonary embolism (PE). The percutaneous catheter-based rheolytic thrombectomy is a promising alternative for management of massive pulmonary emboli, particularly, when patients have contraindication with systemic thrombolysis or are not suitable for surgery.
We present the case of a 36-year-old Somalian man who came to our center for a total knee replacement (TKR). Three days after TKR, he developed sudden shortness of breath and decreased oxygen saturation. Computed tomography of pulmonary arteriogram showed extensive thrombi within the main pulmonary trunk, right and left pulmonary arteries, bilateral ascending and bilateral descending pulmonary arteries in keeping with massive PE. Because the patient was contraindicated for systemic thrombolysis, percutaneous, catheter-based rheolytic thrombectomy was chosen as the alternative treatment. His clinical symptoms improved immediately post-treatment. In conclusion, catheter-based rheolytic thrombectomy can serve as an alternative treatment for massive PE with a good clinical outcome.
PMCID: PMC3744003  PMID: 23983581
thrombectomy; thrombolysis; pulmonary embolism
12.  In Situ Identification of CD44+/CD24− Cancer Cells in Primary Human Breast Carcinomas 
PLoS ONE  2012;7(9):e43110.
Breast cancer cells with the CD44+/CD24− phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24− cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24− population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24− cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%–21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24− cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24− cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24− tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24− cell percentage.
PMCID: PMC3441535  PMID: 23028444
13.  Breast milk expression among formally employed women in urban and rural Malaysia: A qualitative study 
Many women are unable to practice exclusive breastfeeding because they are separated from their infants while working. Expressing their breast milk helps them to continue breastfeeding. This study explores the perception and experiences related to the feasibility, acceptability and safety of breast milk expression among formally employed women in Kelantan, Malaysia.
A qualitative method using in-depth interviews was conducted from December 2008 to December 2009 among Malay women from urban and rural areas. A snowball sampling method was used to recruit the informants, and the interviews, which were facilitated by an interview guide, were audio-recorded and transcribed verbatim. Thematic analysis was conducted, with construction of codes and themes from each interview.
Analysis of the interviews with 20 informants identified three themes related to breast milk expression. The themes were as follows: (i) lack of feasibility of expressing breast milk, (ii) negative feelings about expressing breast milk, and (iii) doubts about the safety and hygiene of expressed breast milk. The informants who did not practice exclusive breastfeeding believed that expressing their breast milk was not feasible, commonly because they felt there were not enough facilities for them. They also had negative feelings such as embarrassment. The safety and hygiene of the expressed breast milk was also their main concern.
More practical and focused education, as well as provision of facilities, is needed for women to effectively and safely express and store their breast milk. The issue of inadequate milk production should be emphasized, especially by encouraging them to express their breast milk as a way to improve milk production.
PMCID: PMC3453522  PMID: 22929649
Breast milk expression; Pumping; Exclusive breastfeeding; Employed; In-depth interview
14.  Fatal mediastinal biopsy: How interventional radiology saves the day 
Annals of Thoracic Medicine  2012;7(2):107-109.
This was a case of a 35-year-old man with mediastinal mass requiring computed tomography (CT)-guided biopsy for tissue diagnosis. A posterior approach with an 18-gauge biopsy needle was used to obtain tissue sample. Post biopsy, patient condition deteriorated and multiphase CT study detected active bleeding in arterial phase at the biopsy site with massive hemothorax. Subsequent angiography showed arterial bleeder arising from the apical branch of the right pulmonary artery. Selective endovascular embolization with NBCA (n-Butyl cyanoacrylate) was successful. Patient survived the complication. The case highlighted a rare complication in a common radiology procedure and the value of the interventional radiology unit in avoiding a fatal outcome.
PMCID: PMC3339201  PMID: 22558017
Biopsy; complications; computed tomography; guidance; mediastinum; therapeutic embolization
15.  Prevalence and Risk Factors of Intestinal Helminth Infection Among Rural Malay Children 
Soil-transmitted intestinal helminth infection is prevalent in rural communities of Malaysia. Risk factors contributing to helminth infections are largely unknown in the country.
To determine the prevalence and risk factors of intestinal helminth infections among children in Beris Lalang, a rural Muslim community of Malaysia.
Settings and Design
In this cross-sectional study, children aged 7-9 years were recruited during the mass Friday prayer at Beris Lalang mosque by trained imams (religious leaders). A standardized questionnaire was used to obtain information on socio-demographic profile, daily hygienic practices, and history of helminth infection.
Out of 79 samples, 29 (37%) were positive for helminthic ova, of which 24 were ova of Trichuris trichiura. Poor education of the mother (primary education or less) (P=0.015), eating raw salad (P=0.03), and no physical activities (P=0.03) were found independent risk factors for the child's helminth infections in univariate analysis. A higher proportion of children with helminth infections complained of tiredness and fatigue compared to those without such infections (36% vs. 12%, P=0.019). In a multivariate analysis of predictors of helminth infection, poor education of the mother (P=0.02) and eating raw salad (P=0.04) remained statistically significant, after controlling for several other potential risk factors.
T. trichiura was the most prevalent intestinal helminth infection in children in rural Malaysia. Risk factors of helminth infection included mother's poor education and eating raw salad and vegetables.
PMCID: PMC3326951  PMID: 22529621
Children; Intestinal helminth; Malaysia; Prevalence; Risk factors
16.  The Prevalence of Metabolic Syndrome According to Various Definitions and Hypertriglyceridemic-Waist in Malaysian Adults 
Metabolic syndrome can be diagnosed according to several different criteria such as the latest International Diabetes Federation (IDF), National Cholesterol Education Program Adult Treatment Program III (NCEP ATPIII), and World Health Organization (WHO). The objectives of this study were to determine the prevalence of metabolic syndrome and the concordance between the above mentioned definition, and hypertriglyceridemic-waist criteria.
This cross sectional study was done in Bachok, Malaysia and involved 298 respondents aged between 18 to 70 years. Multistage random sampling method was used to identify study locations while convenient random sampling method was applied to select individuals. Hypertriglyceridemic waist was defined from an internationally acceptable cut-off criterion. Kappa statistic (κ test) was used to determine the concordance between various definitions and hypertriglyceridemic-waist.
The prevalence of metabolic syndrome based on different definitions was 32.2% (IDF), 28.5% (NCEP ATP III) and 12.4% (modified WHO). The prevalence of hypertriglyceridemic-waist was 19.7% and based on the IDF criteria a total of 97.5% participants with hypertriglyceridemic-waist had metabolic syndrome. The IDF criteria showed the highest concordance with NCEP ATPIII criteria (κ = 0.63), followed by hypertriglyceridemic-waist criteria (κ = 0.62) and WHO criteria (κ = 0.26).
The prevalence of metabolic syndrome was highest using the IDF criteria compared to NCEP ATPIII, modified WHO and hypertriglyceridemic-waist. There was a good concordance of IDF criteria with NCEP ATP III and hypertriglyceridemic-waist criteria.
PMCID: PMC3237265  PMID: 22174962
Hypertriglyceridemic-waist; Metabolic syndrome; Malaysia
17.  The Vanishing Veins: Difficult Venous Access in a Patient Requiring Translumbar, Transhepatic, and Transcollateral Central Catheter Insertion 
Central venous catheter placement is indicated in patients requiring long-term therapy. With repeated venous catheterisations, conventional venous access sites can be exhausted. This case illustrates the expanding role of radiology in managing difficult venous access. We present a case of translumbar, transhepatic, and transcollateral placement of central catheter in a woman with a difficult venous access problem who required lifelong parenteral nutrition secondary to short bowel syndrome. This case highlights the technical aspects of interventional radiology in vascular access management.
PMCID: PMC3328940  PMID: 22589680
central nervous system neoplasms; child; oncology; recurrence; rhabdoid tumour; teratoma
18.  Y-Stent–Assisted Coil Embolisation of Wide-Necked Aneurysms Using a New Fully Retrievable and Detachable Intracranial Stent: Report of Two Cases 
Endovascular treatment of wide-necked aneurysms poses a challenge for the endovascular therapist. The Y-stent–assisted technique has been used for stent-assisted coil embolisation for wide-necked bifurcation aneurysms. This technique has been described for basilar tip aneurysms and middle cerebral artery bifurcation aneurysms using Neuroform and Enterprise stents. We report 2 cases of wide-necked bifurcation aneurysms that were treated with Y-stent–assisted coil embolisation using a new, fully retrievable and detachable intracranial stent (Solitaire AB™). We describe the advantages of a fully retrievable and detachable stent and its feasibility of forming a Y configuration.
PMCID: PMC3328942  PMID: 22589679
endovascular techniques; intracranial aneurysm; neurosurgery; stents; therapeutic embolisation
19.  DUSPs strike again 
Cell Cycle  2011;10(17):2827-2835.
PMCID: PMC3233488  PMID: 21869596
20.  Follice-Stimulating Hormone Receptor Forms Oligomers and Shows Evidence of Carboxyl-Terminal Proteolytic Processing 
Endocrinology  2007;148(5):1987-1995.
FSH receptor (FSHR), a member of the G protein-coupled receptor superfamily, is present in the plasma membrane of ovarian granulosa cells and testicular Sertoli cells. FSH regulates normal ovarian follicle development and spermatogenesis through FSHR. The extracellular domain of FSHR is a weakly associated homodimer in the recently solved crystal structure of FSH in complex with the extracellular domain of FSHR. However, there is currently no biochemical data that demonstrate that FSHR exists as a dimer or higher-order oligomer in cell membranes. A fluorescence resonance energy transfer assay was used to determine whether full-length native FSHR is an oligomer. FSHR-specific monoclonal antibody or Fab fragments, labeled with two different fluorophores, allowed the study of nontagged receptor in situ. Unoccupied FSHR exhibited strong fluorescence resonance energy transfer profiles in situ. Complementary coimmunoprecipitation experiments of myc- or FLAG-tagged FSHR indicated that FSHR forms oligomers early in receptor biosynthesis. No effect of FSH treatment was observed. Thus, immature forms of FSHR, not yet fully processed, were observed to coimmuno-precipitate. An unexpected observation was made that the C-terminal epitope tags are removed from FSHR before arrival at the cell surface. These results provide the first evidence for oligomers of full-length FSHR in situ and for C-terminal proteolytic processing of FSHR and that both events take place during biosynthesis. This may explain how heterozygous mutations in the FSHR gene that affect receptor trafficking may be ameliorated by oligomer formation.
PMCID: PMC3113408  PMID: 17272391
21.  Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients 
PLoS ONE  2011;6(4):e19234.
Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG.
Materials and Methods
We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival.
Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that “RANK-negative” and “RANK-positive” patients had a SDFS of 105.7 months (95% CI: 73.9–124.4) and 58.9 months (95% CI: 34.7–68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029).
This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.
PMCID: PMC3084800  PMID: 21559440
22.  Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes 
The human equilibrative nucleoside transporter 1 (hENT1) is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively). Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036), while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.
PMCID: PMC3167316  PMID: 20839414
human equilibrative nucleoside transporter 1; histotypes; vater ampulla; cancer; immunohistochemistry.
23.  Embolisation of a Bronchial Artery of Anomalous Origin in Massive Haemoptysis 
Massive haemoptysis is the most dreaded of all respiratory emergencies. Bronchial artery embolisation is known to be a safe and effective procedure in massive haemoptysis. Bronchial artery of anomalous origin presents a diagnostic challenge to interventional radiologists searching for the source of haemorrhage. Here, we report a case of massive haemoptysis secondary to a lung carcinoma with the bronchial artery originating directly from the right subclavian artery. This artery was not evident during the initial flush thoracic aortogram. The anomalous-origin bronchial artery was then embolised using 15% diluted glue with good results. An anomalous-origin bronchial artery should be suspected if the source of haemorrhage is not visualised in the normally expected bronchial artery location.
PMCID: PMC3216163  PMID: 22135550
bronchial arteries; glues; haemoptysis; therapeutic embolisation; medical sciences
24.  Reversible splenial lesion syndrome in neuroleptic malignant syndrome 
Reversible focal lesions in the splenium of the corpus callosum (SCC) or reversible splenial lesion syndrome are rare and little is known about their pathophysiology.
Case summary
The authors describe a case of a 65-year-old female who presented with fever, abnormal behaviour and mild hypernatremia. She was on neuropsychiatric treatment for bipolar disorder but denied any history of seizure. After an extensive workout to exclude infection, a clinical diagnosis of neuroleptic malignant syndrome (NMS) was made. Initial magnetic resonance imaging (MRI) of the brain showed a lesion in the SCC characterized by high-signal intensity on T2-weighted and FLAIR sequences with reduced signal intensity on T1-weighted sequence. Diffuse weighted imaging (DWI) showed restricted diffusion. There was no enhancement following Gadolinium administration. The follow-up MRI 8 weeks later showed complete resolution of the SCC lesion.
While the pathophysiology of reversible SCC lesions is still unclear, this case highlights the need to consider NMS in the differential diagnosis of reversible splenial lesion of the corpus callosum.
PMCID: PMC3097717  PMID: 21610992
corpus callosum; reversible splenial; neuroleptic malignant syndrome
25.  Superselective Embolisation in Acute Lower Gastrointestinal Haemorrhage: A Single Institution Experience 
Superselective embolisation has been recognised as integral in the management of lower gastrointestinal haemorrhage. It has also reduced the need for emergency surgery. The objective of this case series was to describe the lower gastrointestinal haemorrhage cases seen in our centre, its diagnosis and the role of superselective embolisation in patient management.
All patients who underwent superselective embolisation from January 2008 until April 2009 in our centre were analysed. Data were collected from the hospital electronic medical records.
Four patients (three males) with a mean age of 81 years were analysed. Multidetector computerised tomography and digital subtraction angiography were positive in all patients. Superselective embolisation with platinum microcoils was performed in all patients (n = 4). Technical success was achieved in all patients (100%).
Superselective embolisation in the treatment of lower gastrointestinal haemorrhage is safe and effective with a very high technical success rate.
PMCID: PMC3216130  PMID: 22135510
gastrointestinal haemorrhage; therapeutic embolisation; spiral computerised tomography; medical sciences

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