Basal cell carcinoma (BCC) develops predominantly in sun-exposed skin in fair-skinned individuals prone to sunburn. BCC typically occurs in adults. High exposure to ultraviolet (UV) radiation increases rate of developing BCC, a slowly growing tumor that occurs in hair-growing squamous epithelium and rarely metastasizes. In genetic studies, BCC patients have cell-cycle abnormalities of different parts of the signaling pathway. Retinoblastoma regulatory pathway is important in cell cycle arrest. In this pathway, p16INK4a, an inhibitor of Rb pathway, binds to CDK4 and CDK6 competitively with cyclin D1 to prevent phosphorylation of tumor suppressor pRB gene. Alteration of this pathway contributes to development of human cancers and also is effective in skin cancers. In this study, we analyzed mRNA expression using in situ RT-PCR and the role of immunohistochemical expression of p16INK4a in BCC.
Burkholderia pseudomallei is the etiological agent of melioidosis, a severe infectious disease of humans and animals. The role of the bacterium's proteins expressed in vivo during human melioidosis continues to remain an enigma. This study's aim was to identify B. pseudomallei target proteins that elicit the humoral immune response in infected humans. A small insert genomic expression library was constructed and immunoscreened to identify peptides that reacted exclusively with melioidosis patients' sera. Sero-positive clones expressing immunogenic peptides were sequenced and annotated, and shown to represent 109 proteins involved in bacterial cell envelope biogenesis, cell motility and secretion, transcription, amino acid, ion and protein metabolism, energy production, DNA repair and unknown hypothetical proteins. Western blot analysis of three randomly selected full-length immunogenic polypeptides with patients' sera verified the findings of the immunome screening. The patients' humoral immune response to the 109 proteins suggests the induction or significant upregulation of these proteins in vivo during human infection and thus may play a role in the pathogenesis of B. pseudomallei. Identification of B. pseudomallei immunogens has shed new light on the elucidation of the bacterium's pathogenesis mechanism and disease severity. These immunogens can be further evaluated as prophylactic and serodiagnostic candidates as well as drug targets.
This study compared the surface hardness, flexural strength, and flexural modulus of a light- and heat-cured urethane dimethacrylate (UDMA) to two conventional polymethyl methacrylate (PMMA) denture base resins. The effect of less-than-optimal processing condition on the hardness of internal and external surfaces of UDMA specimens was also investigated.
INTRODUCTION: Erectile dysfunction (ED), lower urinary tract symptoms (LUTS), cardiovascular disease (CVD), depression, and androgen deficiency are common conditions affecting aging men over 50 years. However, data were limited in developing countries.
AIMS: To investigate the prevalence of ED, LUTS, chronic diseases, depression, androgen deficiency symptoms, and lifestyle of aging men in Malaysia, and to examine their associations with sociodemographic factors.
MAIN OUTCOME MEASURES: ED, LUTS, chronic diseases, depression, positive Androgen Deficiency in the Aging Male (ADAM) questionnaire
METHODS: A randomized survey of 351 men using structured questionnaires consisting of self-reported medical conditions, International Index for Erectile Function-5, International Prostate Symptom Score, Geriatric Depression Scale-15, and St Louis University questionnaire for ADAM. Blood samples were taken for glucose, lipid, prostate specific antigen (PSA), and hormones.
RESULTS: Mean age was 58+/-7 years. Prevalence of ED was 70.1% (mild ED 32.8%, mild to moderate ED 17.7%, moderate ED 5.1%, and severe ED 14.5%). There were 29% of men with moderate and severe LUTS; 11.1% had severe depression; 25.4% scored positive on ADAM questionnaire; 30.2% self-reported hypertension, 21.4% self-reported diabetes mellitus; 10.8% self-reported coronary artery disease; 19.1% were smokers; and 34% consumed alcohol. There were 78.6% of men that are overweight and obese; 28.8% had a fasting blood sugar (FBS) >or=6.1 mmol/L, 70.1% had total cholesterol >5.2 mmol/L, 19.1% had total testosterone >or=11.0 nmoL/L, 14.0% had calculated free testosterone <0.0225 nmoL/dL; 4% had PSA >4 microg/L; 9.4% had insulin-like growth factor-1 (IGF-1) level below age specific range, 5.1% had abnormal sex hormone binding globulin (<15 nmoL/L and >70 nmol/L). ED was found to be significantly associated with LUTS, depression (P<0.001 respectively). Similarly, LUTS was significantly associated with depression and ADAM questionnaire status (P<0.001 respectively); and ADAM questionnaire status was also significantly associated with depression (P<0.001).
CONCLUSION: ED, LUTS, depression, and androgen deficiency symptoms are common in urban aging men. As these conditions are possibly interrelated, strategies for early disease prevention and detection are warranted when one disease presents.
Influenza surveillance in Europe is based on influenza surveillance networks that cooperate and share information through the European Influenza Surveillance Scheme (EISS). EISS collected clinical and virological data on influenza in 33 countries during the 2006-2007 winter. Influenza activity started around 1 January and first occurred in Greece, Scotland and Spain. It then moved gradually across Europe from south to north and lasted until the end of March. In 29 out of 33 countries, the consultation rates for influenza-like-illness or acute respiratory infections in the winter of 2006-2007 were similar or somewhat higher than in the 2005-2006 winter. The highest consultation rates for influenzal ike-illness were generally observed among children aged 0-4 years and 5-14 years. The predominant virus strain was influenza A (97% of total detections) of the H3 subtype (93% of H-subtyped A viruses; 7% were A(H1)). The influenza A(H3) and A(H1) viruses were similar to the vaccine reference strains for the 2006-2007 season, A/Wisconsin/67/2005 (H3N2) and A/New Caledonia/20/99 (H1N1) respectively. The majority of the influenza B viruses were similar to the reference strain B/Malaysia/2506/2004, included in the 2006-2007 vaccine. In conclusion, the 2006-2007 influenza season in Europe was characterised by moderate clinical activity, a south to north spread pattern across Europe, and a dominance of influenza A(H3). Overall there was a good match between the vaccine virus strains and the reported virus strains.
MeSH terms: Adolescent; Adult; Child; Child, Preschool; Europe/epidemiology; Health Status Indicators; Humans; Infant; Infant, Newborn; Influenza, Human/epidemiology*; Influenza, Human/virology*; Middle Aged; Population Surveillance/methods*; Seasons
Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by the SARS coronavirus (SARS-CoV). The development of new antiviral agents for SARS-CoV is an important issue. We tried to find potential resource from Traditional Chinese medicine (TCM) for development of new drugs against SARS-CoV.
MeSH terms: Animals; Antiviral Agents/isolation & purification; Antiviral Agents/pharmacology; Cercopithecus aethiops; Drugs, Chinese Herbal/pharmacology; Drugs, Chinese Herbal/chemistry; Medicine, East Asian Traditional; Plant Extracts/pharmacology*; Vero Cells; Virus Replication/drug effects*; Plant Leaves; Cedrela/chemistry*; SARS Virus/drug effects*
Traditionally peritoneal dialysis (PD) catheter was implanted by surgeons using mini-laparotomy or open technique in Malaysia. We introduced peritoneoscopic Tenckhoff catheter insertion technique since the beginning of our PD program. Data were collected from the start of our PD program in February 2006 until April 2008. All Tenckhoff catheters were inserted by nephrologists using the peritoneoscope technique. We also compare the penetration rate of PD versus hemodialysis (HD) in our center, as well as comparing to national PD penetration rate. There were 83 patients who underwent 91 peritoneoscope Tenckhoff catheter insertion procedures from March 2006 until April 2008. The patients were mostly female (66%) with the mean age of 51.99 +/- 1.78 years and the majority (67%) of them were diabetics. All together there were 749.7 patient-months at risk and the overall peritonitis rate was 1 in 93.7 patient-months. The 1-year catheter survival was 86.5%. Primary catheter failure (defined as failure of the catheter within 1 month of insertion) occurred in 16 procedures (17.6%). The main cause of catheter malfunction was catheter tip migration and omentum wrap. The penetration ratio of PD when compared with HD in our center is 44.8%, which is about 4.5 times the national average. With our integrated care approach where nephrologist was heavily involved from the outset of renal replacement therapy discussion, PD access implantation to the assistance of spoke person to whom new patient can identify with, we were able to achieve PD penetration rate which far exceeds that of the national average.
Nipah virus was first discovered in 1999, after a severe outbreak of viral encephalitis among pig farm workers in Malaysia. The disease is thought to spread from Pteropus bats to pigs and then to humans following close contact. The reported mortality rate in this outbreak was 40%. The main necropsy finding in patients with Nipah virus encephalitis was disseminated microinfarction associated with vasculitis and direct neuronal involvement. Relapse of encephalitis was seen in 10% of those who survived the initial illness. Since that initial report, recurrent outbreaks of Nipah virus encephalitis have been seen in Bangladesh and West Bengal, India. These outbreaks occurred between January and May, with Pteropus giganteus as a reservoir of the virus. In Bangladesh, the virus probably spread directly from bats to humans-with human to human spread as another important mode of infection-and the mortality rate was 70%.
Consecutive chloroform, ethanol, and ethyl acetate partitions of extracts from winged bean [Psophocarpus tetragonolobus (L.) DC] root, stem, leaf, and pod extracts were tested for their antimicrobial activity against 19 microbial species, including 11 bacterial pathogens, four yeasts, and four molds using the disk diffusion assay technique. The pod extract was found to be most effective against all of the tested organisms, followed by the stem, root, and leaf extracts, and the ethanol fraction showed the most significant (p < 0.05) antimicrobial activity against all of the tests among three soluble fractions of extract, followed by the ethyl acetate and chloroform fractions. The minimum inhibitory concentrations (MICs) of extracts determined by the broth dilution method ranged from 1.25 to 10.0 mg/mL. The MIC of ethanol fraction of pod extracts was the lowest by comparison with the other two extracts. The MIC for fungi was at or below 2.5 mg/mL and for bacteria was at or above 2.5 mg/mL.
The articular facets on the inferior aspect of the occipital condyles, articulate with the superior articular facets of the first cervical (atlas) vertebra, to form the atlanto-occipital joint. The present case, reports the asymmetrical dimensions of the facets on the occipital condyles of a human dried skull. The anatomico-radiological study of asymmetrical articular facets on the occipital condyles, may be helpful for academicians, neuro-surgeons, clinicians and radiologists in day to day clinical practice.
BACKGROUND: Breast cancer is the most common cancer and cause of deaths in women around the world. Oncogene amplification usually occurs late in tumor progression and correlates well with aggressiveness of tumor. In fact the function of the S100A4 protein and its role in metastasis is unclear at present. The purpose of the study was to determine the expression of S100A4 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of S100A4 gene product.
METHODS: S100A4 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissue cores from 216 patients.
RESULTS: S100A4 was absent in normal breast tissues while positive in 45.1% of infiltrating ductal carcinoma (IDC) node negative and 48.8% of infiltrating lobular carcinoma node negative. In paired samples, S100A4 protein was expressed in 13.5% of IDC node positive cases and 35.1% of matched lymph node metastasis.
CONCLUSION: S100A4 protein expression appears widely expressed in early and advanced breast cancer stages compared with normal breast. Our study suggests S100A4 may play a role in breast cancer progression and may prove to be an independent marker of breast cancer which appears to be down regulated in more advanced stages of breast cancer.
The aim of our study is to describe the pattern, clinical features, treatment regimes, and disease activity among the patients treated for rheumatoid arthritis (RA) in the Sarawak General Hospital. We performed a cross-sectional study of all patients with a diagnosis of RA who received treatment at the General Medical Clinic and the Rheumatology Clinic in Sarawak General Hospital over a 1-year period from 1st June 2006 to 31st May 2007. Demographic data, clinical features, and disease activity of all 154 patients were collected for statistical analysis. Rheumatoid arthritis afflicts all the major racial groups in Sarawak including the native population. Our patients have a mean disease duration of 5.4 years (SD 5.69) and a mean duration of delay in diagnosis RA and initiation of disease-modifying antirheumatic drug (DMARD) treatment of 42.9 months (SD 60.1). They have a low rate of interstitial lung disease (6.5%) and rheumatoid nodules (4.5%). Rheumatoid factor was positive in 65.5% of our patients. They have a mean Disease Activity Score (DAS) 28 score of 4.28 (SD 1.33). Only 12.5% of our patients are in remission with DAS 28 < 2.6 and 30.9% of our patients are having high disease activity with DAS 28 > 5.1. Despite the high usage of DMARDs in Sarawak (>80%), our patients have severe disease with high disease activity indices. This is most likely due to delay in diagnosis and initiating DMARDs in RA patients in Sarawak.
Study site: General Medical Clinic and the Rheumatology Clinic in Sarawak General Hospital
OBJECTIVE: Drug overdose exposures were compared with chemical poisoning in terms of demographics, associated factors and final outcomes.
METHOD: Deliberate self-poisoning (DSP) cases admitted to Penang General Hospital during the years 2000-2004 were studied. Chi-square, independent t-test and binary logistic were used whenever applicable.
RESULTS: Indian patients were more likely to use household products, whereas Malay and Chinese patients were more likely to take drug overdoses (P=.001). Drug overdose victims experienced more socioeconomic problems (P=.05) and were more likely to be admitted to the intensive care unit (P=.052). Chemical poisoning patients presented earlier (P=.011), were hospitalized for shorter time (P=.001) and had a higher rate of mortality (P=.01).
CONCLUSION: The present study has identified a unique ethnic variation in the choice of suicide attempts from toxic substances. DSP associated with drug overdose showed significant morbidity, but increased mortality was seen in chemical poisoning.
This is a study aimed to examine the distribution pattern of a specific minichromosome maintenance protein 2 (MCM2) in benign and malignant breast tissue. We also aim to correlate the frequency of expression of MCM2 with the degree of tumor differentiation. We used immunohistochemistry to examine the distribution and expression pattern of MCM2 on formalin-fixed paraffin-embedded tissue sections of benign (n = 30) and malignant breast tissue (n = 70) (IDC 56, DCIS 4, ILC 2, nonductal 4, mixed type 4). We quantified MCM2 expression by calculating a labeling index, which represents the percentage of epithelial nuclei that stained positively. Immunoreactivity was heterogenous in all the 70 malignant cases examined. Epithelial cells in cycle are most frequent at the tumor periphery. Labeling index of MCM2 was greatest in grade 3 (poorly differentiated) and lowest in grade 1 tumors (well differentiated). Minichromosome maintenance protein 2 expression in breast cancer showed a positive association with histologic grade (P < .05). In all the benign breast tissue examined, no proliferating compartments could be characterized. Minichromosome maintenance protein 2 is a useful proliferative marker of breast carcinoma. The frequency of expression of MCM2 showed an inverse correlation with the degree of tumor differentiation.
Within Malaysia's otherwise highly accessible public healthcare system, palliative medicine is still an underdeveloped discipline. Government surveys have shown that opioid consumption in Malaysia is dramatically lower than the global average, indicating a failure to meet the need for adequate pain control in terminally ill patients. Indeed, based on daily defined doses, only 24% of patients suffering from cancer pain receive regular opioid analgesia. The main barriers to effective pain control in Malaysia relate to physicians' and patients' attitudes towards the use of opioids. In one survey of physicians, 46% felt they lacked knowledge to manage patients with severe cancer pain, and 64% feared effects such as respiratory depression. Fear of addiction is common amongst patients, as is confusion regarding the legality of opioids. Additional barriers include the fact that no training in palliative care is given to medical students, and that smaller clinics often lack facilities to prepare and stock cheap oral morphine. A number of initiatives aim to improve the situation, including the establishment of palliative care departments in hospitals and implementation of post-graduate training programmes. Campaigns to raise public awareness are expected to increase patient demand for adequate cancer pain relief as part of good care.
MeSH terms: Analgesics, Opioid/therapeutic use; Developing Countries; Drug Utilization/statistics & numerical data; Health Policy; Health Services Accessibility; Humans; Health Knowledge, Attitudes, Practice; Malaysia/epidemiology; Neoplasms/epidemiology; Pain/epidemiology; Pain/prevention & control*; Palliative Care; Practice Patterns, Physicians'; Terminally Ill
BACKGROUND: Monitoring acute postoperative pain as the fifth vital sign is currently practiced in many developed countries. In Sarawak, pain is an important symptom as 70% of cancer patients present with advanced disease. As the existing validated pain assessment tools were found to be difficult to use, we studied the feasibility of modifying the use of a pain assessment tool, consisting of the short form of the Brief Pain Inventory and the Wong-Baker Faces Scale.
METHOD: This tool was used to document pain in all 169 patients who were admitted for pain control to the oncology ward between July 2000 and June 2001. Nurses were trained in the use of the modified scale before the start of the study.
RESULTS: The method was easy to use, and the mean number of days to reduce pain was found to be 3.1 days (SD: 2.9; median: 2 days; range: 1-31 days). At discharge, none in the group with initially mild pain had pain, and the severity of pain for 98% of patients with moderate pain and 61% with severe pain was downgraded to mild pain.
CONCLUSION: The staff found that the tool allowed continuous pain assessment in an objective manner.
MeSH terms: Adolescent; Adult; Aged; Feasibility Studies; Female; Health Plan Implementation; Hospitals, General; Humans; Malaysia; Male; Medical Oncology; Middle Aged; Pain Measurement/methods*; Pain, Postoperative/diagnosis*; Pain, Postoperative/therapy
Seven new indole alkaloids of the Aspidosperma type, jerantinines A-G (1-7), were isolated from a leaf extract of the Malayan Tabernaemontana corymbosa. The structures were established using NMR and MS analysis. Five of the alkaloids isolated and two derivatives (1-5, 8, 9) displayed pronounced in vitro cytotoxicity against human KB cells (IC50 < 1 microg/mL).
1. This study was undertaken to elucidate the effects of inhibiting the renin-angiotensin system (RAS) with losartan, and acute unilateral renal denervation on renal haemodynamic responses to intrarenal administration of vasoconstrictor doses of dopamine and vasodilator doses of isoprenaline in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Acute unilateral renal denervation of the left kidney in rats was confirmed by a drop in the renal vasoconstrictor response to renal nerve stimulation (P < 0.05) along with diuresis and natriuresis. Rats were pretreated with losartan for 7 days and thereafter animals fasted overnight were anaesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and acute renal haemodynamic responses studied. 3. Dose-response curves were constructed for dopamine and isoprenaline that induced falls or increases in renal blood flow, respectively. It was observed that renal vascular responses were greater in the denervated as compared with rats with intact renal nerves (all P < 0.05). Dopamine-induced renal vasoconstrictor responses were markedly lower in losartan-treated denervated WKY and SHR compared with their untreated counterparts (all P < 0.05). It was also observed that in losartan-treated and denervated WKY rats the vasodilatory responses to isoprenaline were markedly lower compared with untreated rats (all P < 0.05). However, in SHR, under the same conditions, there was no difference in the renal response to isoprenaline whether or not rats were treated with losartan (P > 0.05). 4. The data obtained showed that the renal vasoconstrictor effect of dopamine depends on intact renal nerves and RAS in WKY and SHR. Isoprenaline responses were likewise sensitive to renal denervation and RAS inhibition in WKY rats but not SHRs. Our observations reveal a possible relationship between renal AT(1) receptors and alpha(1)-adrenoceptors in WKY and SHR. There is also evidence to suggest an interaction between renal beta-adrenoceptors and AT(1) receptors in WKY rats.
The binding selectivity of the M(phen)(edda) (M=Cu, Co, Ni, Zn; phen=1,10-phenanthroline, edda=ethylenediaminediacetic acid) complexes towards ds(CG)(6), ds(AT)(6) and ds(CGCGAATTCGCG) B-form oligonucleotide duplexes were studied by CD spectroscopy and molecular modeling. The binding mode is intercalation and there is selectivity towards AT-sequence and stacking preference for A/A parallel or diagonal adjacent base steps in their intercalation. The nucleolytic properties of these complexes were investigated and the factors affecting the extent of cleavage were determined to be: concentration of complex, the nature of metal(II) ion, type of buffer, pH of buffer, incubation time, incubation temperature, and the presence of hydrogen peroxide or ascorbic acid as exogenous reagents. The fluorescence property of these complexes and its origin were also investigated. The crystal structure of the Zn(phen)(edda) complex is reported in which the zinc atom displays a distorted trans-N(4)O(2) octahedral geometry; the crystal packing features double layers of complex molecules held together by extensive hydrogen bonding that inter-digitate with adjacent double layers via pi...pi interactions between 1,10-phenanthroline residues. The structure is compared with that of the recently described copper(II) analogue and, with the latter, included in molecular modeling.