Our objective was to determine the survival and prognostic factors of motor neuron disease (MND) in a multi-ethnic cohort of Malaysian patients. All patients seen at a university medical centre between January 2000 and December 2009 had their case records reviewed for demographic, clinical and follow-up data. Mortality data, if unavailable from records, were obtained by telephone interview of relatives or from the national mortality registry. Of the 73 patients, 64.4% were Chinese, 19.2% Malays and 16.4% Indians. Male: female ratio was 1.43: 1. Mean age at onset was 51.5 + 11.3 years. Onset was spinal in 75.3% and bulbar in 24.7% of the patients; 94.5% were ALS and 5.5% were progressive muscular atrophy (PMA). Overall median survival was 44.9 + 5.8 months. Ethnic Indians had shorter interval from symptom onset to diagnosis and shorter median survival compared to non-Indians. On Cox proportional hazards analysis, poor prognostic factors were bulbar onset, shorter interval from symptom onset to diagnosis and worse functional score at presentation. In conclusion, age of onset and median survival duration are similar to previous reports in Asians. Clinical features and prognostic factors are similar to other populations. In our cohort, ethnic Indians had more rapid disease course accounting for their shorter survival.
The efficacy of allicin compared with fluconazole in alleviating systemic Candida albicans infections was evaluated both in vitro and in vivo through a systemic candidiasis mouse model. Determination of in vitro minimum inhibitory concentrations (MICs) for different C. albicans isolates revealed that both allicin and fluconazole showed different MICs that ranged from 0.05 to 12.5 μg mL(-1) and 0.25 to 16 μg mL(-1) , respectively. A time-kill study showed a significant effect of allicin (P<0.01) against C. albicans, comparable to that of fluconazole. Scanning electron microscopy observation revealed that, similar to fluconazole, allicin produced structural destruction of C. albicans cell surface at low MIC and lysis or puncture at high MIC concentrations. Treatment of BALB/c mice systemically infected with C. albicans showed that although the allicin treatment (at 5 mg kg(-1) day(-1) ) was slightly less efficacious than fluconazole treatment in terms of the fungal load reduction and host survival time, it was still effective against C. albicans in terms of mean survival time, which increased from 8.4 to 15.8 days. These results demonstrate the efficacy of anticandidal effects of allicin both in vitro and in an animal model of candidiasis and affirm the potential of allicin as an adjuvant therapy to fluconazole.
Major reconstructive surgery may be extensive and prolonged, and it may cause edema and compromise the flap pedicle if closed under tension. Glycerol-preserved skin allograft (GPA) can provide a means for tension-free closure and temporary cover of the wound. Seven years of analysis on GPA used in conjunction with major reconstruction was undertaken to highlight its indications, results, and outcomes. Forty-seven patients were included, aged between 9 and 73 years. Majority of patients had reconstruction following tumor resection and trauma. The main indication for use of GPA was temporary, loose cover of the wound in 44% of cases; flap pedicle protection in 31% of cases; donor site wound cover in 10%; flap monitoring in one case; and management of flap-related complications in 6% of cases. Free flap reconstruction was performed in 72% of cases. In conclusion, GPA is a useful adjunct in reconstructive surgery. It can be used temporarily to allow tension-free wound closure, as well as to protect the flap pedicle until edema subsides and the pedicle becomes stable. This latter approach allows secondary wound closure and good esthetic outcome.
INTRODUCTION: Neutropenia has a detrimental effect on cancer patients' quality of life, also possibly resulting in a reduction in the chemotherapy dose which could lead to an increment in the size of a cancer. The main danger associated with neutropenia is the risk of bacterial, fungal or viral infection, which may lead to patient death. Treatment including granulocyte-colony stimulating factors (G-CSF, filgrastim) so as to increase the body immunity is given to neutropenic patients with no infection i.e., absence of fever. However, when infection is present, antibiotics such as ceftazidime, imipenem and vancomycin need to be used.
OBJECTIVE: The aim of this study was to find the association between neutropenia severity and treatment with filgrastim (Neupogen) alone or in combination with antibiotics in solid cancer patients.
METHODS: This is an observational retrospective study on 117 cases suffering from neutropenia after chemotherapy administration. The patients were admitted to a government hospital for cancer treatment between the years 2003-2006. The types of data collected were categorical and not normally distributed, covering demography, chemotherapy, severity of neutropenia (classified on absolute neutrophil count into mild, moderate and severe) and treatment of neutropenia, either filgrastim (Neupogen) alone or in combination with antibiotics. Statistical tests used were the Chi-square test, Fisher's exact test and logistic regression.
RESULTS: The majority (69.2%) of the patients were treated with filgrastim (81) alone, only 30.8% receiving the combination. Significant associations between both treatments and neutropenia severity. Both Chi-square and Fisher's exact tests showed P= 0.001. Logistic regression showed that filgrastim is the major treatment for severe neutropenic patients since the result showed an infinity (E) and P= 0.001 for filgrastim alone more than its combination with antibiotic.
CONCLUSION: The use of filgrastim is highly associated with treatment of severe neutropenia in solid cancer patients who received chemotherapy. So filgrastim is considered as the drug of choice in the presence of severe neutropenic cases.
We studied women with cervical cancer to determine whether they had had a Pap smear within the 3 years preceding cancer development and their understanding of screening for this cancer. The study had 2 parts; Pathology Data and Survey Data. For pathology data, all cases of cervical cancer diagnosed in 2000-2006 were retrieved from eight hospitals and Pap smear history was obtained from clinical records. For the Survey data; patients who were still undergoing treatment in some of these hospitals and three others were administered structured questionnaires to determine their awareness about screening. The results showed 1431 cases of cervical cancer in women aged 25-85 were diagnosed in these hospitals. Most had not had a Pap smear within 3 years before cancer development. The percentages of patients who had had Pap smear ranged from 0-12%. Questionnaires were returned by 221 patients; 56.3% had none or only primary education and 61.1% had a household income of RM 1,000 or less. Level of education and the household income were strongly associated (p<0.05) with knowledge and having had a Pap test. The main reasons cited for not having had a Pap smear were "Never heard about it" (36.2%), "Shy" (10.4%), "Afraid to do it" (13.1%), "Think the test is not important" (8.1%) and "No encouragement from family" (4.5%). A large majority (95.9%) of the patients did not know the optimal interval. In conclusion, a large number of cervical cancer patients had not had a Pap smear within 3 years preceding cancer development and most had inadequate knowledge about this screening test.
p53 is the most commonly mutated tumour-suppressor gene in human cancers. Unlike other tumour-suppressor genes, most p53 cancer mutations are missense mutations within the core domain, leading to the expression of a full-length mutant p53 protein. Accumulating evidence has indicated that p53 cancer mutants not only lose tumour suppression activity but also gain new oncogenic activities to promote tumourigenesis.
BACKGROUND: In Malaysia, acute leukemia is the most common cancer among children below the age of 15. A case-control study was here conducted for cases from the Klang Valley, Malaysia, who received treatment at the National University of Malaysia Hospital (HUKM) and Kuala Lumpur General Hospital (GHKL). The main objective was to determine any association with environmental factors.
METHODS: Case subjects were children aged below 15 years and diagnosed with acute leukemia in HUKM and GHKL between January 1, 2001 and May 30, 2007. Control subjects were children aged below 15 years who were diagnosed with any non-cancerous acute illnesses in these hospitals. A total of 128 case subjects and 128 control subjects were enrolled in this study. The information was collected using a structured questionnaire and a global positioning system (GPS) device. All factors were analyzed using unmatched logistic regression.
RESULTS: The analysis showed that the occurrence of acute leukemia among children was strongly determined by the following factors: family income (odds ratio (OR) 0.19, 95% confidence interval (CI): 0.09-0.42), father with higher social contact (OR 7.61, 95% CI: 3.78-15.4), number of elder siblings (OR 0.36, 95% CI: 0.18-0.77), father who smokes (OR 2.78, 95% CI: 1.49-5.16), and the distance of the house from a power line (OR 2.30, 95% CI: 1.18-4.49).
CONCLUSIONS: Some socioeconomic, demographic, and environmental factors are strong predictors of the occurrence of acute leukemia among children in Klang Valley, Malaysia. In terms of environmental factors, it is recommended that future housing areas should be developed at least 200 m away from power lines.
OBJECTIVE: Kelantan in Malaysia has a high prevalence of diabetes and colorectal cancer is also on the rise. This study is to determine the association of metabolic diseases, particularly diabetes type 2 [DM2] and hypertension, with colorectal cancer patients in our population.
METHODS: This retrospective study was conducted on all colorectal carcinomas in Hospital Universiti Sains Malaysia (HUSM) in Kelantan from ythe ears 2001-2006. The data were retrieved from the Registry in Pathology laboratory and the clinical details from the patients' clinical records and analyzed using SSPS Version 12.0, with a value of p<0.05 taken to be statistically significant.
RESULTS: 138 CRC cases with complete clinical records were included. The age ranged from 16.0 to 88.0 years, with a mean of 56.9 -/+ SD 15.4. The male 90(65%) to female 48(35%) ratio was 1.7:1.0 and 47.8% were suffering from metabolic diseases; 18(13.0%) with Diabetes Mellitus Type 2(DM2), and 48(34.8%) with hypertension (HT). Diabetes Type 2 and hypertension also demonstrated significant association (p<0.05) with the stage and the site of the cancer. Patients with diabetes type 2 88.8%(16/18) and Hypertension 85.4% (41/48) were strongly associated with cancers located in the distal to transverse colon (p<0.001).
CONCLUSION: There is a high proportion of metabolic diseases; hypertension and diabetes type 2 among colorectal carcinomas seen in Kelantan population. In this preliminary study we noted a strong association of metabolic diseases with the stage and site of the cancer. To reduce CRC incidence, the high prevalence of DM2 in Kelantan needs to be addressed.
INTRODUCTION: Mastectomy is an essential but disfiguring operation in cancer treatment. The negative impact on body image can however be prevented by immediate reconstruction.
AIM: The aim of this study was to determine the reasons why patients choose to have or not to have immediate breast reconstruction.
METHODOLOGY: This is a cross sectional descriptive study of breast cancer patients post-mastectomy who had and had not undergone immediate breast reconstruction. The patients were asked a series of questions to ascertain the reasons why they chose or did not choose immediate breast reconstruction.
RESULTS: 136 patients in total were interviewed of which 23 had undergone immediate breast reconstruction. 36.8% of the patients had been offered reconstruction. In the non-reconstructed group, the main reason for not having reconstruction were fear of additional surgery. In the group that had reconstruction done, the main reason was to feel whole again. Low on the list were reasons such as trying to improve marital or sexual relations.
CONCLUSION: Only a third of patients undergoing mastectomy were offered immediate reconstruction. In public hospitals in developing countries, limited operating time and availability of plastic surgery services are major barriers to more women being offered the option.
Our preliminary results indicated that fibrin and poly(lactic-co-glycolic acid) (PLGA) hybrid scaffold promoted early chondrogenesis of articular cartilage constructs in vitro. The aim of this study was to evaluate in vivo cartilaginous tissue formation by chondrocyte-seeded fibrin/PLGA hybrid scaffolds. PLGA scaffolds were soaked carefully, in chondrocyte-fibrin suspension, and polymerized by dropping thrombin-calcium chloride (CaCl2) solution. PLGA-seeded chondrocytes were used as a control. Resulting constructs were implanted subcutaneously, at the dorsum of nude mice, for 4 weeks. Macroscopic observation, histological evaluation, gene expression and sulphated-glycosaminoglycan (sGAG) analyses were performed at each time point of 1, 2 and 4 weeks post-implantation. Cartilaginous tissue formation in fibrin/PLGA hybrid construct was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan and glycosaminoglycan (GAG) in fibrin/PLGA hybrid constructs was confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene encoded cartilage-specific markers, collagen type II and aggrecan core protein. The sGAG production in fibrin/PLGA hybrid constructs was higher than in the PLGA group. In conclusion, fibrin/PLGA hybrid scaffold promotes cartilaginous tissue formation in vivo and may serve as a potential cell delivery vehicle and a structural basis for articular cartilage tissue-engineering.
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. The SMN2 gene is highly homologous to SMN1 and has been reported to be correlated with severity of the disease. The clinical presentation of SMA varies from severe to mild, with three clinical subtypes (type I, type II, and type III) that are assigned according to age of onset and severity of the disease. Here, we aim to investigate the potential association between the number of copies of SMN2 and the deletion in the NAIP gene with the clinical severity of SMA in patients of Malaysian origin. Forty-two SMA patients (14 of type I, 20 type II, and 8 type III) carrying deletions of the SMN1 gene were enrolled in this study. SMN2 copy number was determined by fluorescence-based quantitative polymerase chain reaction assay. Twenty-nine percent of type I patients carried one copy of SMN2, while the remaining 71% carried two copies. Among the type II and type III SMA patients, 29% of cases carried two copies of the gene, while 71% carried three or four copies of SMN2. Deletion analysis of NAIP showed that 50% of type I SMA patients had a homozygous deletion of exon 5 of this gene and that only 10% of type II SMA cases carried a homozygous deletion, while all type III patients carried intact copies of the NAIP gene. We conclude that there exists a close relationship between SMN2 copy number and SMA disease severity, suggesting that the determination of SMN2 copy number may be a good predictor of SMA disease type. Furthermore, NAIP gene deletion was found to be associated with SMA severity. In conclusion, combining the analysis of deletion of NAIP with the assessment of SMN2 copy number increases the value of this tool in predicting the severity of SMA.
Matched MeSH terms: Survival of Motor Neuron 2 Protein
This is a study on 124 patients who were treated by the authors over a 19-year period. There were 48 male and 76 female patients. The age range of these patients at the time of treatment was between 4 months and 32 years. There was no family history of similar deformity. All of these patients come from a socially low-income group. Fourteen patients had accompanying congenital amputation of fingers, toes, or limbs. Two had oral cleft lip and palate. The surgical treatment was medial orbital wall osteotomy and excision of encephalocele. There were two mortalities and five patients who had complications that needed secondary surgical intervention. Thirty-eight patients are still under follow up without any complaints.
Spinal Muscular Atrophy (SMA) is an autosomal recessive disease, which is characterized by degeneration of the anterior horn cells of the spinal cord. SMA is classified into 3 clinical subtypes, type I (severe), type II (intermediate), and type III (mild). Two genes, SMN1 and NAIP, have been identified as SMA-related genes. The SMN1 gene is now recognized as a responsible gene for the disease because it is deleted or mutated in most SMA patients. However, the role of the NAIP gene in SMA has not been fully clarified. To clarify the contribution of NAIP to the disease severity of SMA, we studied the relationship between NAIP-deletion and clinical phenotype in Malaysian patients. A total of 39 patients lacking SMN1 (12 type I, 19 type II, and 8 type III patients) were enrolled into this study. Seven out of 12 patients with type I SMA (approximately 60%) showed NAIP deletion. On the contrary, only 2 out of 20 type II patients and none of type III patients showed NAIP deletion. There was a statistically significant difference in NAIP-deletion frequency among the clinical subtypes (Fisher's exact probability test, p value = 0.014). In conclusion, according to our data that NAIP deletion was more frequent in type I SMA than in type II-III SMA, the NAIP gene may be a modifying factor for disease severity of SMA.
Matched MeSH terms: Survival of Motor Neuron 1 Protein
The survival motor neuron 1 (SMN1) gene has been recognized to be responsible for spinal muscular atrophy (SMA) because it is homozygously deleted in more than 90% of SMA patients, irrespective of their clinical severity, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is now considered to be a modifying factor of the severity of SMA. In Malaysia, it remains to be elucidated whether deletion of the SMN1 gene is also a main cause of SMA or whether deletion of the NAIP gene is found in the SMA patients.
Matched MeSH terms: Survival of Motor Neuron 1 Protein
Breast cancer is the most common female cancer and the commonest cause of death due to cancer for women in Malaysia. This study was performed to identify the relationship with lifestyle factors. A case-control study was conducted among females with breast cancer who came for treatment to the Breast Clinic Hospital Kuala Lumpur in July until September 2004. A total of 203 female patients were recruited as cases along with 203 patients who attended the Outpatient Clinic, Hospital Kuala Lumpur during the study period as the controls. The study showed women who did not exercise regularly to have four times higher risk (adjusted odds ratio is 3.49, 95% CI is 1.84 to 6.62) compared to those who exercised regularly. Women with a high fat diet were also at elevated risk (adjusted odds ratio 3.84, 95% CI is 1.20 to 12.34) compared to those consuming a low fat diet. Women without breast cancer generally had a longer duration of lifetime lactation with a median of thirty-three months compared to women with breast cancer (twenty months, p<0.05). Women who did not take oral contraceptive pills but had breast-fed their child have a 56.0% lower risk (crude odds ratio 0.44, CI is 0.22 to 0.87) compared to women who did not take oral contraceptive pill and also did not breast-feed their child. If they had breast fed for thirteen months and above, they faced a 61.0% lower risk (crude odds ratio 0.39, 95% CI is 0.17 to 0.87). There was a significant inverse trend for lifetime lactation and breast cancer risk. In conclusion certain life styles of women are associated with a higher risk of breast cancer development. Therefore, the promotion of a healthy life style should be emphasized.
Study site: Breast Clinic, Outpatient clinic, Hospital Kuala Lumpur, Malaysia
Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score.
Numerous preclinical and clinical studies have investigated the regenerative potential and the trophic support of mesenchymal stem cells (MSCs) following their injection into a target organ. Clinicians favor the use of smallest bore needles possible for delivering MSCs into vascular organs like heart, liver and spleen. There has been a concern that small needle bore sizes may be detrimental to the health of these cells and reduce the survival and plasticity of MSCs.