Diabetic foot infection and surgical treatment in a secondary health care centre in Malaysia.

INTRODUCTION: Diabetic foot infection is often associated with high morbidity, disability and poor quality of life. This study focuses on the demography, the number of repetitive surgery and length of stay in hospital of patients with diabetic foot infection. METHOD: This is a retrospective observational study. Patients who were admitted to the Orthopaedic ward of Hospital Segamat (HS), Johor, Malaysia from January 2016 to December 2018 and required surgical intervention were included in the study. Data was collected from the computer system of HS and medical notes of patients. RESULTS: 35.6% of the total orthopaedic emergency surgeries performed were for patients with diabetic foot infection, 25% of the surgical procedures performed were major amputations of lower limb and 40% of the patients with diabetic foot infection required more than one surgical operation. DISCUSSION: The demographics of the patients is consistent with the demographics of Malaysia where majority of them are Malays followed by Chinese, Indians and others. Despite being only 10% of total admission to the department, this group of patients contributed to 35.6% of the total emergency surgeries performed. The amputation rate in the centre is comparable to the other local studies. The average length of stay in hospital was found to be shorter compared to overseas due to different rehabilitation protocols.

Necrotising fasciitis caused by aeromonas sobria: Not just a simple catfish sting.

Necrotising fasciitis is a life-threatening infection of the soft tissue which can be caused by different microorganisms, but infection caused by Aeromonas spp. or Vibrio spp. is frequently associated with higher mortality rate. Necrotising fasciitis progresses rapidly and often need aggressive surgical intervention. We present a rare case of necrotising fasciitis cause by Aeromonas sobria which mortality was successfully prevented by swift diagnosis and aggressive surgery.

Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer.

INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene. MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies. RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent. CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate.

INTRODUCTION: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. METHODS: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. RESULTS: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). CONCLUSION: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.

Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA.

AIMS: To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished. METHODS: Tissue sections from the central nervous system of infected cases were examined by light microscopy, immunohistochemistry and in situ hybridization. RESULTS: All 13 cases of EV71 encephalomyelitis collected from Asia and France invariably showed stereotyped distribution of inflammation in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus and, to a lesser extent, cerebral cortex and meninges. Anterior pons, corpus striatum, thalamus, temporal lobe, hippocampus and cerebellar cortex were always uninflamed. In contrast, the eight JE cases studied showed inflammation involving most neuronal areas of the central nervous system, including the areas that were uninflamed in EV71 encephalomyelitis. Lesions in both infections were nonspecific, consisting of perivascular and parenchymal infiltration by inflammatory cells, oedematous/necrolytic areas, microglial nodules and neuronophagia. Viral inclusions were absent. CONCLUSIONS: Immunohistochemistry and in situ hybridization assays were useful to identify the causative virus, localizing viral antigens and RNA, respectively, almost exclusively to neurones. The stereotyped distribution of inflammatory lesions in EV71 encephalomyelitis appears to be very useful to help distinguish it from JE.

In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease.

Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.

Coxsackievirus A16 in a 1-Day-Old Mouse Model of Central Nervous System Infection Shows Lower Neurovirulence than Enterovirus A71.

Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are the major causes of hand, foot and mouth disease in young children. Although less so with CV-A16, both viruses are associated with serious neurological syndromes, but the differences between their central nervous system infections remain unclear. We conducted a comparative infection study using clinically-isolated CV-A16 and EV-A71 strains in a 1-day-old mouse model to better understand the neuropathology and neurovirulence of the viruses. New serotype-specific probes for in situ hybridization were developed and validated to detect CV-A16 and EV-A71 RNA in infected tissues. Demonstration of CV-A16 virus antigens/RNA, mainly in the brainstem and spinal cord neurons, confirmed neurovirulence, but showed lower densities than in EV-A71 infected animals. A higher lethal dose50 for CV-A16 suggested that CV-A16 is less neurovirulent. Focal virus antigens/RNA in the anterior horn white matter and adjacent efferent motor nerves suggested that neuroinvasion is possibly via retrograde axonal transport in peripheral motor nerves.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asians with chronic pulmonary disease: a pilot study.

BACKGROUND: Little is known about the relationship between cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asian patients and severe asthma or idiopathic bronchiectasis. We investigated this potential relationship in the Singaporean Chinese. METHODS: Twenty patients with chronic pulmonary disease, 14 with severe asthma and 6 with idiopathic bronchiectasis, were screened for CFTR mutations by direct gene sequencing. The frequencies of identified putative mutations were compared against 40 unaffected controls and 96 unselected population samples. RESULTS: Three missense mutations (I125T, I556V, and Q1352H) and 1 splice site variant (intron 8 12TG5T) were identified in a total of 10 patients, representing a combined mutant/variant allele frequency of 0.25. These alleles were also observed in the controls, but at a significantly lower allele frequency of 0.09 (P<0.01). Furthermore, the I125T mutation was significantly associated with the idiopathic bronchiectasis sub-group (P<0.05). CONCLUSIONS: The significantly higher frequency of CFTR mutations among patients with chronic pulmonary disease compared with unaffected controls suggests that these mutations may increase risk for disease. The association of I125T with idiopathic bronchiectasis alone suggests that different mutations predispose to different disease.

Insulinomimetic effects of myricetin on lipogenesis and glucose transport in rat adipocytes but not glucose transport translocation.

Myricetin is a naturally occurring flavonol that is commonly found in tea, berries, fruits, and medicinal plants. It mimics insulin in stimulating lipogenesis and glucose transport in rat adipocytes in vitro. It was found to stimulate lipogenesis in rat adipocytes and enhance the stimulatory effect of insulin. The EC50 was estimated to be about 65 microM. Myricetin did not have any effect on insulin receptor autophosphorylation nor on the tyrosine kinase activity of the receptor. However, myricetin stimulated both D-glucose and D-3-O-methylglucose uptake in rat adipocytes. The Vmax of glucose transport was increased, but the Km did not change significantly. Immunoblot analysis of Glut4 in rat adipocyte plasma membrane showed that the stimulation of glucose transport was not a consequence of glucose transporter translocation. Instead, the stimulation in glucose uptake probably was due to a change in the intrinsic activity of the glucose transporter possibly caused by alterations in membrane fluidity or transporter-lipid interactions as a result of the insertion of myricetin into the membrane bilayer. Thus, myricetin may have therapeutic potential in the management of non-insulin-dependent diabetes mellitus by stimulating glucose uptake without the presence of fully functional insulin receptor.

Effects of myricetin on glycemia and glycogen metabolism in diabetic rats.

In our previous study, we found that myricetin, a naturally occurring bioflavonoid, was able to stimulate glucose transport in rat adipocytes and enhance insulin-stimulated lipogenesis. We report here that after 2 days of treatment with myricetin (3 mg/12 h), hyperglycemia in diabetic rats was reduced by 50% and the hypertriglyceridemia that is often associated with diabetes was normalised. Treatment with myricetin increased hepatic glycogen and glucose-6-phosphate content. It increased hepatic glycogen synthase I activity without having any effect on total glycogen synthase nor phosphorylase a activity. It lowered phosphorylase a activity in the muscle. Thus, the hypoglycemic effect of myricetin is likely to be due to its effect on glycogen metabolism. There was no indication of serious hepatotoxicity with myricetin treatment and therefore, myricetin could be of therapeutic potential in diabetes.

Comparison of the severity of sleep-disordered breathing in Asian and Caucasian patients seen at a sleep disorders center.

Race can be considered a risk factor for sleep-disordered breathing (SDB), with higher prevalences and greater severity of the disorder documented among persons of certain racial groups compared with others. Based on clinical observation, it was hypothesized that, other risk factors being equal, Asian patients with SDB have greater severity of their illness compared to Caucasian patients. A cross-sectional study was conducted at a sleep disorders clinic involving 105 Asian patients diagnosed as having SDB after undergoing polysomnography and 99 similarly diagnosed Caucasian patients matched for the following variables: age, gender and body mass index (BMI). The main outcome measure of interest was objective assessment of severity based on polysomnographic data of respiratory disturbance index (RDI) and minimum oxygen saturation (SaO2) during sleep. Symptom scores between patients of the two racial groups were also compared. There were significantly larger proportions of Asians compared to Caucasians with severe obstructive sleep apnea (OSAS) as defined by respiratory disturbance index (RDI) > or = 50 (25.0% vs 11.1%; P = 0.0288) or minimum oxygen saturation (SaO2) < or = 69% (20.6% vs 4.2%; P = 0.0113). The mean minimum SaO2 was significantly lower (P = 0.0001) while the mean (log transformed) esophageal pressure (Pes) value was significantly higher (P = 0.0090) in the Asian group. Logistic regression analysis showed that race was associated with severe SDB (RDI > or = 50) independent of age, sex and BMI. The estimated odds ratio for Asians having severe OSAS compared with Caucasians was 2.51 [95% Confidence Interval (CI) 0.98-6.64]. There was no significant difference in the severity of questionnaire-based symptoms of snoring, apneas during sleep and the median Epworth scores between Asian and Caucasian patients. Based on objective polysomnographic results, Asian patients with OSAS have greater severity of their illness compared to Caucasian patients matched for age, gender and BMI. There was, however, no significant difference in severity of questionnaire-based symptoms between Asian and Caucasian patients with SDB.

Community-acquired pneumonia.

Major changes have occurred in the epidemiology of community-acquired pneumonia recently. The emergence of new pathogens emphasises the need for continued vigilance in the diagnosis of pneumonia while changes in the microorganism or in the host have resulted in exciting new aspects of several old pathogens. Clinical and radiologic signs are unreliable in predicting the infecting organisms. Thus initial therapy is nearly always empiric. This approach often requires good clinical judgement and a knowledge of local epidemiological patterns in choosing an appropriate regimen. State-of-the-art invasive diagnostic procedures are usually reserved for pneumoniae that fail to resolve with initial treatment. Non-specific measures like stabilisation of underlying medical conditions, adequate nutrition and cessation of smoking or alcohol may help prevent the development of community-acquired pneumonia. On a larger scale, influenza and pneumococcal vaccinations are cost-effective preventive measures.

The diagnostic yield of pleural fluid cytology in malignant pleural effusions.

BACKGROUND: The development of a pleural effusion in a patient with a known malignancy often raises the possibility that the effusion is due to malignant involvement of the pleura. Accurate diagnosis of the cause of the pleural effusion in such a patient is essential as the treatment and prognosis may vary. Currently, thoracentesis and cytologic analysis of pleural fluid cytology is usually the initial diagnostic step. AIM: To assess the diagnostic yield of pleural fluid cytologic examination in patients with suspected malignant pleural effusions seen at our centre. METHODS: Retrospective review of the results of pleural fluid cytologic examination performed on 103 patients who presented with suspected malignant pleural effusions. RESULTS: The underlying malignancies in these patients were as follows: bronchogenic carcinoma (51.5%), breast carcinoma (29.1%), hepatocellular carcinoma (1.9%), carcinoma of the stomach (1.9%), malignant mesothelioma, nasopharyngeal carcinoma, renal cell carcinoma, carcinoma of the oesophagus, lymphoma, carcinoma of the colon (1% each), unknown (9.7%). Initial pleural fluid cytology was positive for malignancy in 48.5% of patients. The yield of this diagnostic procedure was improved with repeated pleural fluid cytologic specimens and when combined with a percutaneous pleural biopsy. There was no statistically significant difference in the clinical features and pleural fluid characteristics of patients with malignant pleural effusions and those in whom the pleural effusions were paramalignant. CONCLUSION: Pleural fluid cytologic examination is a useful initial step in the diagnostic work-up of patients with suspected malignant pleural effusions. The diagnostic yield of such examination is improved with repeated pleural fluid cytologic specimens and when combined with a percutaneous pleural biopsy. Clinical presentation and pleural fluid characteristics were inadequate in differentiating between malignant and paramalignant effusions.

Neuroleptic malignant syndrome without neuroleptics.

Neuroleptic malignant syndrome is an uncommon condition characterised by hyperthermia, rigidity, altered mentation and autonomic instability. Recognition of this condition is essential because its complications are potentially lethal, leading to death in 20% of patients. Not all cases of this syndrome are associated with the use of neuroleptics and there is an increasing number of reports of this condition occurring after withdrawal of therapy with dopaminergic drugs, typically in patients with Parkinsonism. In this setting, there is tremendous potential for misdiagnosis and delay in institution of treatment because of the traditional and common association of the syndrome with the use of neuroleptics only. We report a case of neuroleptic malignant syndrome in a patient with Parkinsonism subsequent to the withdrawal of levodopa and bromocriptine.

Cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Accurate assessment of the exercise capacity of patients with chronic obstructive pulmonary disease (COPD) is important for the dual purpose of exercise prescription and determining response to therapy. Currently, the clinical utility of cardiopulmonary exercise testing (CPET) of patients with COPD as part of their evaluation for pulmonary rehabilitation is not established. The aims of this study were to evaluate the role of CPET in determining maximal exercise capacity and the causes of exercise limitation in patients with COPD. MATERIALS AND METHODS: The results of resting pulmonary function tests and CPET performed on 33 subjects with stable COPD as part of their evaluation for pulmonary rehabilitation were reviewed. Thirty-two of these patients had moderate or severe COPD. RESULTS: Twenty-nine of the 33 patients were able to perform maximal exercise tests during CPET. Of these 29 maximal tests, the causes of exercise limitation were ventilatory limitation in 17 patients, significant oxygen desaturation in 1 patient and both ventilatory limitation and oxygen desaturation in 11 patients. Limb muscle dysfunction is a possible limiting factor in the 4 patients with sub-maximal tests. Physical deconditioning may be a contributory factor of exercise intolerance in 2 patients. Although there was significant correlation (r = 0.597, P = 0.01) between peak VO2 percent predicted and FEV1 percent predicted, there was marked variability of peak VO2 for a given degree of airflow obstruction. CONCLUSIONS: CPET is useful for determining the causes of exercise limitation and for assessing the maximal exercise capacity of patients with COPD.

Upper airway resistance syndrome--report of three cases.

INTRODUCTION: Patients with the upper airway resistance syndrome are frequently overlooked, and even if clinically suspected, often escape identification by polysomnographic monitoring. CLINICAL PICTURE: Three cases (2 women and a man) with excessive daytime sleepiness and fatigue were confirmed to have the upper airway resistance syndrome after undergoing polysomnography with oesophageal pressure monitoring. TREATMENT: Nasal CPAP during sleep was prescribed for 2 cases but 1 case refused all available treatment options. OUTCOME: After one month of CPAP therapy, the 2 cases reported improved symptoms and Epworth sleepiness scores. Lower daytime blood pressures were also recorded. CONCLUSIONS: Oesophageal pressure monitoring and EEG arousal analysis can greatly enhance the diagnostic accuracy in the upper airway resistance syndrome. Accurate diagnosis and effective treatment of this condition is important because of its sequelae of hypersomnolence and association with other disorders like systemic hypertension.

Ideal endotracheal tube placement by referencing measurements on the tube.

The ideal position of the endotracheal tube (ETT) within the trachea is 5 +/- 2 cm from the carina with the head and neck in neutral position (Goodman's criteria). We assessed the possibility of achieving ideal placement of ETTs in our population by positioning them at reference marks of 23 cm in men and 21 cm in women. From January 1995 to April 1995, 105 intubated patients in the Medical Intensive Care Unit, Singapore General Hospital were studied. The mean distance of the ETT tip from the carina was 4.02 cm +/- 3.90. The ETT tip was < 3 cm from the carina in 30 cases (28.6%) with one case resulting in endobronchial intubation. These 30 patients were significantly shorter in height when compared to the rest of the study population (P = 0.01). Five cases (4.8%) had ETT tip > 7 cm from the carina. Adopting the above-mentioned reference marks did not result in ideal positioning of ETTs in a significant proportion of cases (33.4%). We postulate that this is because our Asian population is generally shorter than those in previous studies which had achieved ideal ETT positioning using similar reference marks.

Noninvasive positive-pressure ventilation for acute respiratory failure in a medical intensive care unit in Singapore.

The main advantage of noninvasive ventilation over conventional mechanical ventilation is in the avoidance of endotracheal intubation and its related complications. Currently, the role of noninvasive ventilation in the management of patients with acute respiratory failure is still not firmly established. We conducted a prospective study to evaluate the efficacy of nasal positive pressure ventilation in patients with acute respiratory failure. Thirty-three consecutive patients with acute failure in whom intubation and mechanical ventilation were strongly considered were included in the study. They received ventilatory support by means of BiPAP ventilatory support system and nasal mask. Physical findings and laboratory measurements were documented before and at specific intervals after initiation of support. Eighty per cent (24/30) of patients were successfully supported. Successfully supported patients tolerated the device with improved gas exchange, hence avoiding endotracheal intubation. The mean duration of support was 19.2 hours. There were major associated complications, e.g. gastric distention or aspiration.

Active management of a patient with endstage pulmonary emphysema using lung volume reduction surgery and intensive rehabilitation.

INTRODUCTION: Lung volume reduction surgery (LVRS) and pulmonary rehabilitation are newer options available in the treatment of advanced emphysema. We describe the progress of our first local patient to have undergone these 2 new treatment modalities. CLINICAL PICTURE: A 65-year-old man with advanced emphysema, limited by crippling dyspnoea despite maximal medical therapy with inhaled bronchodilator therapy, methylxanthines and supplementary oxygen. TREATMENT: Physical reconditioning with a 4-week inpatient pulmonary rehabilitation programme, followed by LVRS and a further 6-week outpatient pulmonary rehabilitation. OUTCOME: Dramatic improvements in spirometric indices, arterial blood gases, exercise capacity and overall functional status. Improvements maintained at one-year follow up period. CONCLUSIONS: LVRS with pulmonary rehabilitation is an exciting new treatment option in a select group of patients with advanced emphysema. Their role in improving overall performance status and quality of life should be considered in patients otherwise considered to have reached the limits of medical therapy.