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1.
Aust Vet J ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009477

ABSTRACT

A 12-year-old female spayed Domestic Shorthair cat presented with a 4-day history of lethargy, inappetence and vomiting. Physical findings included a grade 2/6 heart murmur and cranial abdominal pain on palpation. Serum biochemistry revealed elevated total bilirubin and liver enzymes activities. Abdominal ultrasound revealed multiple pancreatoliths, cholelithiasis and dilation of the pancreatic duct. During exploratory laparotomy, catheterisation of the pancreatic duct with retrograde and orthograde flushing to remove the pancreatoliths was performed via a distal enterotomy and proximal left apical partial pancreatectomy respectively. Catheterisation and flushing of the common bile duct were performed to confirm patency prior to cholecystectomy. Bacterial culture of pancreatoliths, pancreatic tissue and bile grew a heavy, pure growth of Providencia rettgeri. Fluorescent immunostaining histopathology revealed clusters of rod-shaped bacteria within the pancreatic parenchyma and gall bladder mucosa. The cat received pradofloxacin for two weeks. She made a complete recovery and remained well at a six-month follow-up.

2.
Med J Malaysia ; 76(6): 820-827, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34806667

ABSTRACT

INTRODUCTION: Despite the ever-growing number of community onset (CO) Pseudomonas aeruginosa (P. aeruginosa) bacteraemia, there is a dearth of district hospital-based research examining this significant infection, which is associated with high mortality. The objectives of this study were as following: (1) to determine the risk factors of CO P. aeruginosa bacteraemia, (2) to compare the 30-day mortality rate between P. aeruginosa and Escherichia coli bacteraemia and (3) to identify the predictors of 30-day mortality for CO gram negative bacteraemia. METHODS: This is a retrospective case control study in Hospital Seri Manjung and Hospital Teluk Intan, Perak, Malaysia. P. aeruginosa bacteraemia cases that occurred between 1st January 2015 to 31st December 2019 were included, whilst E. coli bacteraemia cases that occurred within the same period were recruited successively until 1:2 case control ratio was achieved. Subjects below 12-year-old and those with polymicrobial bacteraemia were excluded. Demographic, clinical and treatment data were collected using pre-tested data collection forms by trained investigators. RESULTS: A total of 61 patients with P. aeruginosa bacteraemia and 122 patients with E. coli bacteraemia were included. Recent admission in the earlier three months, regular haemodialysis, immunosuppressive therapy in the past 30 days, chronic wound/pressure sore at presentation and indwelling urinary catheter at presentation were identified as independent predictors of CO pseudomonal bacteraemia. Whilst older age was identified as a negative predictor of CO Pseudomonal bacteraemia (all p<0.05). The 30-day mortality rate was 34.4% in subjects with P. aeruginosa bacteraemia and 27.0% in those with E. coli bacteraemia (p=0.302). Predictors of 30-day mortality for community onset gram negative bacteraemia were as follow: older age, underlying solid tumours, neutropaenia at presentation, in-patient mechanical ventilation, and inpatient nasogastric tube insertion. Unexpectedly, receipt of inappropriate empirical antibiotics which was switched later (delayed and non-delayed switching) was identified as the negative predictors of mortality (all p<0.05). CONCLUSION: It is prudent to restrict the usage of empirical anti-pseudomonal antibiotics among individuals at risk as liberal usage of broad-spectrum antibiotics engenders emergence of drug resistant organism, particularly in district setting where community onset pseudomonal bacteraemia remains scarce. Subjects with elevated risk of mortality should receive early escalation of care as per sepsis management guidelines.


Subject(s)
Bacteremia , Pseudomonas aeruginosa , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/epidemiology , Case-Control Studies , Child , Escherichia coli , Hospitals, District , Humans , Retrospective Studies , Risk Factors
3.
Med J Malaysia ; 76(1): 24-28, 2021 01.
Article in English | MEDLINE | ID: mdl-33510104

ABSTRACT

INTRODUCTION: COVID-19 is a highly transmissible respiratory virus that has affected millions of people worldwide in the span of months. The burden of disease among healthcare workers (HCW) has not been well studied despite reports of infectivity and transmission around the world. Two HCW in Hospital Teluk Intan (HTI) contracted COVID-19 while attending a social event. They were in close proximity with colleagues upon returning to work, resulting in the spread of infection among other HCW in HTI. OBJECTIVE: The objectives of this paper are to gain a better understanding of the key presenting symptoms of COVID-19 in HCWs in a district specialist hospital, to establish the proportion of symptomatic COVID-19 cases among HCWs and its severity and to determine the time taken from onset of symptoms or perceived exposure to diagnostic testing. METHODOLOGY: This is a retrospective descriptive analysis of clinical characteristics of subjects infected with COVID-19 among HCW in HTI. Their demography and clinical characteristics were recorded. RESULTS: There were 47 HCW in HTI who tested positive for COVID-19. The mean age of the patients was 37.5 years old. 7 patients (15.2%) had at least more than one comorbidity. Average duration of time from perceived close contact to onset of symptom was 4.5 days, while the mean duration of time from symptoms to first positive RT-PCR result was 3.4 days. Six patients (13.0%) were asymptomatic throughout, whereas 40 (87.0%) had at least one symptom prior to hospitalization. The most commonly reported symptoms were fever (65.2%), sore throat (39.1%) and cough (37.0%). In terms of severity of symptoms, the majority of patients experienced mild symptoms (Group 2, 52.2%). Two patients (4.3%) with multiple comorbidities had severe disease requiring ICU admission and mechanical ventilation. There were no mortalities, and the longest staying patient was hospitalized for 18 days. The high rates of infectivity among HCW in HTI can be attributed to working in close proximity while in the asymptomatic incubation phase, while no HCW directly involved in the care of COVID-19 positive patients were tested positive. CONCLUSION: We report that HCW share similar clinical characteristics of COVID-19 infection as those of non HCW patients in earlier studies. The infection can spread rapidly within healthcare settings via close contacts among infected HCWs. As such, we advocate distancing when working and usage of personal protective equipment when treating patients with respiratory illness to reduce transmission of COVID-19.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Occupational Exposure , Personnel, Hospital/statistics & numerical data , Adult , Asymptomatic Infections , COVID-19/complications , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Comorbidity , Cough/virology , Critical Care/statistics & numerical data , Female , Fever/virology , Hospitals, District , Humans , Length of Stay/statistics & numerical data , Malaysia/epidemiology , Male , Middle Aged , Patient Acuity , Pharyngitis/virology , Prodromal Symptoms , Retrospective Studies , SARS-CoV-2 , Time Factors
4.
Med J Malaysia ; 75(4): 356-362, 2020 07.
Article in English | MEDLINE | ID: mdl-32723994

ABSTRACT

OBJECTIVE: Problematic smartphone use (PSU) is the development of pathological dependence at the expense of performing activities of daily living, thus having negative health and psychological impact on the users. Previous PSU studies focused on medical students and little is known regarding its effect on students undergoing other courses. The objective of this study is to identify the pattern of smartphone usage and determine the psychological factors affecting PSU among undergraduate students in Malaysia and compare the pattern among students from different fields of study. METHOD: A prospective cross-sectional study was conducted using the validated Smartphone Addiction Scale-Malay version (SAS-M) questionnaire. One-way ANOVA was used to determine the correlation between the PSU among the students categorised by their ethnicity, hand dominance and by their field of study. MLR analysis was applied to predict PSU based on socio-demographic data, usage patterns, psychological factors and fields of study. RESULTS: A total of 1060 students completed the questionnaire. Most students had some degree of problematic usage of the smartphone. Students used smartphones predominantly to access SNAs, namely Instagram. Longer duration on the smartphone per day, younger age at first using a smartphone and underlying depression carried higher risk of developing PSU, whereas the field of study (science vs. humanities based) did not contribute to an increased risk of developing PSU. CONCLUSION: Findings from this study can help better inform university administrators about at- risk groups of undergraduate students who may benefit from targeted intervention designed to reduce their addictive behaviour patterns.


Subject(s)
Smartphone , Students , Universities , Cross-Sectional Studies , Female , Humans , Malaysia , Male , Mental Health , Prospective Studies , Surveys and Questionnaires
5.
Br J Oral Maxillofac Surg ; 58(7): 812-818, 2020 09.
Article in English | MEDLINE | ID: mdl-32409131

ABSTRACT

Is there a variation in facial ideals depending on ethnic background that affects judgements of outcome in orthognathic surgery? How does the evaluation correlate with patient-reported outcome measures? Two evaluation panels, Singaporean and Swedish, judged photographs of patients undergoing orthognathic surgery taken before and after operation. Improvement in facial aesthetics was calculated between the two ratings. The result was compared between the panels and correlated with health-related quality of life (QoL) measures. Thirty male and 27 female patients aged between 18 and 28 years (mean 21) were included, and 52 subjects were eligible for comparison of health-related QoL. The photographic evaluation showed that both panels judged there to be significant improvement in facial aesthetics after treatment (p<0.001). The Singaporean panel rated the overall facial appearance higher than the Swedish panel when evaluating photographs both before (p=0.025) and after (p=0.032) operation. Improvement of the overall facial appearance showed no significant difference between the panels (p>0.30). No correlation between health-related QoL and improvement of facial appearance was found by either panel. Subjective evaluation of facial aesthetics in orthognathic surgery is unaffected by the observer's ethnic origin. Independently of their ethnicity, the evaluation juries found that facial aesthetics improved after orthognathic surgery. Improvement reported by the juries corresponded to that reported by patients.


Subject(s)
Orthognathic Surgery , Orthognathic Surgical Procedures , Adolescent , Adult , Esthetics, Dental , Ethnicity , Female , Humans , Male , Quality of Life , Young Adult
6.
Med J Malaysia ; 75(1): 62-67, 2020 01.
Article in English | MEDLINE | ID: mdl-32008023

ABSTRACT

OBJECTIVE: To identify regions of the brain affected during cognitive working memory during tasks to assess attention, planning and decision making among military aviation personnel who have chronic intermittent exposure to high altitude environment. METHOD: A case-control study was conducted in the Universiti Putra Malaysia among eight military personnel, four of whom had chronic intermittent exposure to high altitude training. They were divided into two groups, chronic intermittent exposure group (CE) (n=4) and a control group (n=4). They underwent a task-based functional magnetic resonance imaging (fMRI) that utilised spatial working memory task to objectively evaluate the neural activation in response to the Tower of London paradigm. Each correct answer was given a score of one and the maximum achievable score was 100%. RESULTS: A consecutive dichotomised group of CE (4/8) and control (4/8) of age-matched military aviation personnel with a mean age of 37.23±5.52 years; showed significant activation in the right middle frontal gyrus (MFG). This in turn was positively correlated with response accuracy. A significant difference in the response accuracy was noted among both the groups at p<0.05. CONCLUSION: At the minimum results of power analysis of this preliminary fMRI study, our group of aviation personnel who had chronic intermittent exposure to hypobaric hypoxic environment, did not have any significant decrease in cognitive function namely attention, decision-making and problem solving compared to controls during a working memory task.


Subject(s)
Cognition , Hypoxia/psychology , Military Personnel/psychology , Adult , Aviation , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Malaysia , Male , Memory, Short-Term , Neuroimaging
7.
Malays Orthop J ; 14(3): 4-9, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33403056

ABSTRACT

The recent coronavirus disease (COVID-19) was declared as a public health emergency by the World Health Organisation on 30th January 2020, and has now affected more than 100 countries. Healthcare institutions and governments worldwide have raced to contain the disease, albeit to varying degrees of success. Containment strategies adopted range from complete lockdowns to remaining open with public advisories regarding social distancing. However, general principles adopted by most countries remain the same, mainly to avoid gatherings in large numbers and limit social interactions to curb the spread of disease. In Singapore, this disease had a very different progression. The first wave of the disease started with the confirmation of the first COVID-19 positive patient in Singapore on 23rd January 2020. Initially, the daily number of confirmed cases were low and manageable. With a rise in unlinked cases, the Disease Outbreak Response System Condition (DORSCON) status was raised from yellow to orange. New cluster outbreaks in foreign worker dormitories led to the rampant spread of disease, with daily spikes of COVID-19 cases. As of 7th June 2020, we have a total of 37,910 confirmed cases of COVID-19 infections, the highest in Southeast Asia, 12,999 active cases and a manageable mortality count of 25 deaths. This details our unique method for dealing with a pandemic, including a brief demographic of trauma patients during this period. We were able to conserve sufficient resources to ensure that our essential services can still continue. Moving on, we have to ensure the continued protection of our population, especially the vulnerable groups such as the elderly and the immunocompromised, as we reopen.

8.
Br J Oral Maxillofac Surg ; 58(1): 43-50, 2020 01.
Article in English | MEDLINE | ID: mdl-31718913

ABSTRACT

Submental intubation is a low-risk alternative to tracheostomy when nasotracheal or orotracheal intubation is not appropriate. To improve the selection of patients and clinical outcomes we have explored published papers on submental intubation in oral and maxillofacial surgery, and included a proposal for a decision pathway. Systematic searches of PubMed, Scopus, and Cochrane databases for papers published between 1986 and 2018 yielded 116 eligible articles (one randomised controlled trial, 61 case series, 40 case reports, six surgical techniques, and eight letters) that included 2 229 patients. Measured outcomes were the indications, techniques, devices used, time taken to complete the procedure, and complications. Indications were trauma (81%), orthognathic surgery (15%), disease (2%), and cosmetic surgery (1%). Technical preferences were for a one-tube (84%) over a two-tube technique (6%), and a paramedian (52%) over a median incision (33%). The preferred device was a reinforced endotracheal tube (85%). The mean (range) intubation time was 10 (2-37) minutes. The complication rate was 7% (n=152), the most common being superficial skin infection (n=54), hypertrophic scarring (n=18), and damage to the tube apparatus (n=15). Submental intubation has minimal complications, takes a short time to do, and it is a useful alternative to tracheostomy in some oral and maxillofacial operations. More robust evidence regarding the selection of patients, modifications to the technique, and a comparison of risk with that of tracheostomy, are needed for further evaluation of its feasibility.


Subject(s)
Intubation, Intratracheal , Maxillofacial Injuries/surgery , Surgery, Oral , Facial Bones , Humans , Tracheostomy
9.
Article in English | WPRIM (Western Pacific) | ID: wpr-837558

ABSTRACT

@#The recent coronavirus disease (COVID-19) was declared as a public health emergency by the World Health Organisation on 30th January 2020, and has now affected more than 100 countries. Healthcare institutions and governments worldwide have raced to contain the disease, albeit to varying degrees of success. Containment strategies adopted range from complete lockdowns to remaining open with public advisories regarding social distancing. However, general principles adopted by most countries remain the same, mainly to avoid gatherings in large numbers and limit social interactions to curb the spread of disease. In Singapore, this disease had a very different progression. The first wave of the disease started with the confirmation of the first COVID-19 positive patient in Singapore on 23rd January 2020. Initially, the daily number of confirmed cases were low and manageable. With a rise in unlinked cases, the Disease Outbreak Response System Condition (DORSCON) status was raised from yellow to orange. New cluster outbreaks in foreign worker dormitories led to the rampant spread of disease, with daily spikes of COVID-19 cases. As of 7th June 2020, we have a total of 37,910 confirmed cases of COVID-19 infections, the highest in Southeast Asia, 12,999 active cases and a manageable mortality count of 25 deaths. This details our unique method for dealing with a pandemic, including a brief demographic of trauma patients during this period. We were able to conserve sufficient resources to ensure that our essential services can still continue. Moving on, we have to ensure the continued protection of our population, especially the vulnerable groups such as the elderly and the immunocompromised, as we reopen.

10.
Int J Oral Maxillofac Surg ; 48(8): 1001-1008, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30922629

ABSTRACT

This retrospective study was performed to review 1038 patients who underwent mandibular reconstruction with free vascularized bone flaps at a single institution between 2006 and 2017. Of these patients, 827 (79.67%) had fibula flaps, 197 (18.98%) had deep circumflex iliac artery perforator (DCIA) flaps, and 11 (1.06%) had scapula bone flaps. The most common pathological diagnosis was ameloblastoma (n=366, 35.26%), followed by squamous cell carcinoma (n=278, 26.78%) and osteoradionecrosis (n=152, 14.64%). Fifty-seven patients (5.49%) had major complications requiring surgical intervention and one patient died of a pulmonary embolism. Venous crisis was the most frequent major complication (n=20, 1.93%), followed by haematoma (n=17, 1.64%) and flap necrosis (n=14, 1.35%). One-stage mandibular reconstruction was preferred whenever possible, as this generally decreases the financial and hospitalization burden. The four-segment method of jaw reconstruction appeared to achieve good aesthetic appearance results in Asian patients and this was not associated with a higher risk of segment ischemia compared with the three-segment method.


Subject(s)
Free Tissue Flaps , Mandibular Reconstruction , Osteoradionecrosis , Plastic Surgery Procedures , Fibula , Humans , Retrospective Studies
11.
Herz ; 44(8): 750-755, 2019 Dec.
Article in English | MEDLINE | ID: mdl-29666900

ABSTRACT

BACKGROUND: The polymer-free biolimus-A9 drug-coated stent (DCS) was reported to have superior safety and efficacy outcomes compared with a bare metal stent in the LEADERS FREE trial of high-bleeding-risk patients with acute coronary syndrome and on dual antiplatelet treatment (DAPT) for 1 month. The aim of this investigation was to evaluate the DCS in a consecutive cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). METHODS: We analyzed data from 164 consecutive STEMI patients who underwent PPCI using the DCS at our institution. The primary efficacy endpoint was clinically indicated target lesion revascularization (ciTLR); the primary safety endpoint was a composite of cardiac death, myocardial infarction, and definite/probable stent thrombosis. Clinical outcomes at 1 year are presented here. RESULTS: The mean age of the patients was 61.5 ± 15.5 years, and 86.6% were male. The median symptom-to-balloon-time was 55 min. In 57.9% of patients (n = 95), the infarct had an anterior location. PPCI achieved Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 163 of 164 patients (99.4%). All patients were prescribed DAPT for 1 year. At 1 year, ciTLR occurred in 1.2% of patients, the primary safety endpoint was reached in 4.3% of patients, and definite stent thrombosis was noted in 0.6% of patients. CONCLUSION: In this consecutive real-world cohort of patients, the DCS was safe and efficacious when used for PPCI in patients with STEMI.


Subject(s)
Percutaneous Coronary Intervention , Stents , Aged , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors , Polymers , Prosthesis Design , Risk Factors , Treatment Outcome
12.
Herz ; 44(5): 419-424, 2019 Aug.
Article in English | MEDLINE | ID: mdl-29340719

ABSTRACT

BACKGROUND: Lesion length is a major predictor of adverse outcomes after percutaneous coronary intervention. Long lesions often require multiple stents with variable overlap, which increases the probability of geographical miss and the incidence of mechanical complications, such as side-branch occlusion, restenosis, and stent thrombosis. These pitfalls may be avoided by use of an ultra-long device. METHODS: We retrospectively assessed the performance of the 48-mm Xience Xpedition everolimus-eluting stent (EES) at our institution. RESULTS: A total of 123 patients (mean age: 60.94 years, n = 93 [76%] male) with 129 lesions were identified. Lesions (n = 69, 53.5%) were located in the left anterior descending artery, the right coronary artery (n = 47, 36.4%), and the circumflex artery (n = 8, 6.2%); 83 lesions involved a major side branch. The majority were treated with a provisional single-stent strategy. Other characteristics included significant tortuosity in 15 lesions (11.6%) and moderate-to-heavy calcification in 46 lesions (35.7%). In all cases, balloon pre-dilatation was performed before stent insertion. Successful delivery and deployment of the 48-mm EES device was achieved in 100% of the patients. The mean number of stents per lesion was 1.4, while the mean total stent length was 58 ± 17.3 mm and mean stent diameter, 3.00 ± 0.67 mm. The procedural success rate was 99.2%. The 30-day major cardiac adverse event (MACE) rate was 0.8%, while the 12-month MACE was 3.3%. CONCLUSION: The Xience 48-mm EES device appears to be safe and efficacious with a low clinical event rate at the 12-month follow-up. Where feasible, this would support the use of the ultra-long 48-mm platform in lieu of multiple overlapping shorter devices.


Subject(s)
Cardiovascular Agents , Coronary Artery Disease , Drug-Eluting Stents , Myocardial Infarction , Percutaneous Coronary Intervention , Coronary Artery Disease/therapy , Everolimus , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Paclitaxel , Prosthesis Design , Retrospective Studies , Sirolimus , Treatment Outcome
15.
Clin Microbiol Infect ; 23(9): 677.e1-677.e3, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28336383

ABSTRACT

OBJECTIVES: To determine if emm pattern-inferred tissue tropisms of Group A streptococcus strains is reflected in their ability to adhere to immortalized human HaCat (keratinocyte) and Detroit 562 (pharyngeal) cell lines. METHODS: Human epithelial cell line monolayers were inoculated with Group A streptococcus, and the percentage of adhered bacteria after a 1-h incubation period was calculated. RESULTS: Of the 21/69 inferred-skin-tropic, and the 25/69 inferred-throat-tropic isolates no preferential adherence was observed to a particular cell line. The 23/69 strains classified as 'generalists', however, showed an overall greater ability to adhere to both cell lines. CONCLUSIONS: Predicted tissue-tropism based on emm patterns is not reflected by preferential adherence to a specific cell line, suggesting that early adhesion events may not be as important in establishing infection at a particular ecological niche than originally expected.


Subject(s)
Bacterial Adhesion/physiology , Streptococcus pyogenes/physiology , Streptococcus pyogenes/pathogenicity , Viral Tropism/physiology , Antigens, Bacterial , Bacterial Outer Membrane Proteins , Carrier Proteins , Cell Line , Epithelial Cells/cytology , Epithelial Cells/microbiology , Humans , Pharynx/cytology , Skin/cytology
16.
Mult Scler Relat Disord ; 9: 62-7, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27645347

ABSTRACT

BACKGROUND: There is substantial overlap between MRI of acute spinal cord lesions from neuromyelitis optica (NMO) and spinal cord infarct (SCI) in clinical practice. However, early differentiation is important since management approaches to minimize morbidity from NMO or SCI differ significantly. OBJECTIVE: To identify MRI features at initial presentation that may help to differentiate NMO acute myelitis from SCI. METHODS: 2 board-certified neuroradiologists, blinded to final diagnosis, retrospectively characterized MRI features at symptom onset for subjects with serologically-proven NMO (N=13) or SCI (N=11) from a single institution. Univariate and multivariate analyses were used to identify factors associated with NMO or SCI. RESULTS: SCI was more common in men and Caucasians, while NMO was more common in non-Caucasian women (P<0.05). MRI features associated with NMO acute myelitis (P<0.05) included location within 7-cm of cervicomedullary junction; lesion extending to pial surface; 'bright spotty lesions' on axial T2 MRI; and gadolinium enhancement. Patient's age, lesion length and cross-sectional area, cord expansion, and the "owl's eyes" sign did not differ between the two groups (P>0.05). CONCLUSION: Along with patient demographic characteristics, lesion features on MRI, including lesion location, extension to pial border and presence of 'bright spotty lesion' can help differentiate acute myelitis of NMO from SCI in the acute setting.


Subject(s)
Infarction/diagnostic imaging , Magnetic Resonance Imaging , Neuromyelitis Optica/diagnostic imaging , Spinal Cord Diseases/diagnostic imaging , Spinal Cord/blood supply , Spinal Cord/diagnostic imaging , Adult , Diagnosis, Differential , Female , Humans , Infarction/epidemiology , Male , Middle Aged , Neuromyelitis Optica/epidemiology , Retrospective Studies , Sex Factors , Spinal Cord Diseases/epidemiology
17.
Br J Pharmacol ; 171(13): 3255-67, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24597478

ABSTRACT

BACKGROUND AND PURPOSE: The testing of anticancer compounds in vitro is usually performed in hyperglycaemic cell cultures, although many tumours and their in vivo microenvironments are hypoglycaemic. Here, we have assessed, in cultures of tumour cells, the effects of reduced glucose levels on resistance to anticancer drugs and investigated the underlying cellular mechanisms. EXPERIMENTAL APPROACH: PIK3CA mutant (AGS, HGC27), and wild-type (MKN45, NUGC4) gastric cancer cells were cultured in high-glucose (HG, 25 mM) or low-glucose (LG, 5 mM) media and tested for sensitivity to two cytotoxic compounds, 5-fluorouracil (5-FU) and carboplatin, the PI3K/mTOR inhibitor, PI103 and the mTOR inhibitor, Ku-0063794. KEY RESULTS: All cells had increased resistance to 5-FU and carboplatin when cultured in LG compared with HG conditions despite having similar growth and cell cycle characteristics. On treatment with PI103 or Ku-0063794, only the PIK3CA mutant cells displayed increased resistance in LG conditions. The PIK3CA mutant LG cells had selectively increased p-mTOR, p-S6, p-4EBP1, GLUT1 and lactate production, and reduced reactive oxygen species, consistent with increased glycolysis. Combination analysis indicated PI103 and Ku-0063794 were synergistic in PIK3CA mutant LG cells only. Synergism was accompanied by reduced mTOR signalling and increased autophagy. CONCLUSIONS AND IMPLICATIONS: Hypoglycaemia increased resistance to cytotoxic agents, especially in tumour cells with a high dependence on glycolysis. Dual inhibition of the PI3K/mTOR pathway may be able to attenuate such hypoglycaemia-associated resistance.


Subject(s)
Antineoplastic Agents/pharmacology , Glucose/metabolism , Phosphatidylinositol 3-Kinases/genetics , Stomach Neoplasms/drug therapy , Antineoplastic Agents/administration & dosage , Autophagy/drug effects , Carboplatin/pharmacology , Cell Line, Tumor , Class I Phosphatidylinositol 3-Kinases , Drug Resistance, Neoplasm , Drug Synergism , Fluorouracil/pharmacology , Furans/pharmacology , Glycolysis/physiology , Humans , Hypoglycemia/metabolism , Morpholines/pharmacology , Phenotype , Pyridines/pharmacology , Pyrimidines/pharmacology , Signal Transduction/drug effects , Stomach Neoplasms/pathology , TOR Serine-Threonine Kinases/metabolism
19.
Zentralbl Chir ; 139(4): 452-9, 2014 Aug.
Article in German | MEDLINE | ID: mdl-23460108

ABSTRACT

BACKGROUND: Meckel's diverticulum (MD) is the most common diverticulum of the small bowel and an important finding in surgical practice. The aim of this study was to assess the safety of the resection of symptomatic and asymptomatic MD concerning postoperative complications. As MD are relatively rare, an overview of the literature is given. PATIENTS AND METHODS: All patients with MD at the department at general surgery of the Charité - Campus Benjamin Franklin between 1996 and 2010 were assessed. An analysis for symptomatic and incidental MD was performed for incidence, indication, intraoperative findings, histology and postoperative outcome. RESULTS: An MD was intraoperatively found in 71 of 29 682 patients (0.2 %). Of these, a symptomatic MD occurred in 26 patients (37 %). A symptomatic MD was causal in 6 of 7 patients with gastrointestinal bleeding (GIB, p = 0.005). All symptomatic MD and 30 (67 %) asymptomatic MD were resected. Ectopic gastric mucosa was found significantly more frequently in patients with symptomatic MD (p = 0.001). Patients with asymptomatic MD and resection had less complications as a trend (p = 0.057). CONCLUSION: Ectopic mucosa is more frequent in symptomatic MD, especially in bleeding MD. MD should always be considered in GIB of unknown origin. Resection of incidental MD can be recommended in patients without contraindications such as peritonitis, cancer, ascites or immunosuppression.


Subject(s)
Meckel Diverticulum/diagnosis , Meckel Diverticulum/surgery , Postoperative Complications/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Choristoma/diagnosis , Choristoma/pathology , Choristoma/surgery , Diagnosis, Differential , Female , Follow-Up Studies , Gastric Mucosa , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Humans , Ileal Diseases/diagnosis , Ileal Diseases/pathology , Ileal Diseases/surgery , Ileum/pathology , Ileum/surgery , Incidental Findings , Intestinal Mucosa , Male , Meckel Diverticulum/pathology , Middle Aged , Retrospective Studies , Young Adult
20.
Ir Med J ; 106(8): 235-8, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24282892

ABSTRACT

The objective of this study was to assess appropriate thromboprophylaxis prescription rates in a university hospital and to re-audit after a series of interventions. The notes of all acute medical patient admissions over a 4-week period were assessed for VTE risk factors and prescription of thromboprophylaxis. Subsequently, a series of hospital wide interventions including educational initiatives and a new drug prescription chart were introduced. 2 years post intervention the audit was repeated. Pre-intervention, 104 of 265 (39%) "at risk" patients were prescribed appropriate thromboprophylaxis. Post intervention the prescription rate increased to 108 of 188 (57%) "at risk patients". The results of the pre- intervention audit are consistent with the published literature. While there was a significant increase in prescription rates post intervention, over 40% of "at risk" patients still did not receive thromboprophylaxis highlighting the challenge in attempting to close the gap between guidelines and actual practice.


Subject(s)
Anticoagulants/therapeutic use , Emergency Service, Hospital/organization & administration , Hospitals, University/organization & administration , Inpatients , Medical Audit , Venous Thromboembolism/prevention & control , Cross-Sectional Studies , Female , Humans , Inpatients/statistics & numerical data , Ireland/epidemiology , Male , Middle Aged , Prospective Studies , Risk Assessment , Risk Factors , Venous Thromboembolism/epidemiology
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