A 5-year retrospective study of melioidosis cases treated in a district specialist hospital.

INTRODUCTION: Melioidosis is caused by Burkholderia pseudomallei, a gram-negative aerobic bacillus, found in the soil and surface water. Treating melioidosis has been a challenge in district hospitals due to high usage of broad spectrum antibiotics and prolonged hospitalisation. This study is to review the patients' demography, clinical presentations and microbiological data. METHODS: A 5-year retrospective study was carried out on patients admitted with culture positive for melioidosis from year 2013 to 2017 in Hospital Teluk Intan, Perak. RESULTS: There were a total of 46 confirmed cases of melioidosis. Majority of the patients were working in the agricultural and farming (28.6%), and factories (25.7%). Thirty-one patients had diabetes mellitus (71.1%). Presentations of patients with melioidosis included pneumonia (54.3%), skin and soft tissue infection (19.6%), deep abscesses (15.2%) and bone and joint infections (13%). An average of 5.8 days was needed to confirm the diagnosis of melioidosis via positive culture. However, only 39.4% of these patients were started on ceftazidime or carbapenem as the empirical therapy. The intensive care unit (ICU) admission rate for melioidosis was 46% and the mortality rate was 52%. Our microbial cultures showed good sensitivity towards cotrimoxazole (97.1%), ceftazidime (100%) and carbapenem (100%). CONCLUSION: Melioidosis carries high mortality rate, especially with lung involvement and bacteremia. Physicians should have high clinical suspicion for melioidosis cases to give appropriate antimelioidosis therapy early.

Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

The current treatment landscape of irritable bowel syndrome in adults in Hong Kong: consensus statements.

OBJECTIVE: The estimated prevalence of irritable bowel syndrome in Hong Kong is 6.6%. With the increasing availability of pharmacological and non-pharmacological treatments, the Hong Kong Advisory Council on Irritable Bowel Syndrome has developed a set of consensus statements intended to serve as local recommendations for clinicians about diagnosis and management of irritable bowel syndrome. PARTICIPANTS: A multidisciplinary group of clinicians constituting the Hong Kong Advisory Council on Irritable Bowel Syndrome-seven gastroenterologists, one clinical psychologist, one psychiatrist, and one nutritionist-convened on 20 April 2017 in Hong Kong. EVIDENCE: Published primary research articles, meta-analyses, and guidelines and consensus statements issued by different regional and international societies on the diagnosis and management of irritable bowel syndrome were reviewed. CONSENSUS PROCESS: An outline of consensus statements was drafted prior to the meeting. All consensus statements were finalised by the participants during the meeting, with 100% consensus. CONCLUSIONS: Twenty-four consensus statements were generated at the meeting. The statements were divided into four parts covering: (1) patient assessment; (2) patient's psychological distress; (3) dietary and alternative approaches to managing irritable bowel syndrome; and (4) evidence to support pharmacological management of irritable bowel syndrome. It is recommended that primary care physicians assume the role of principal care provider for patients with irritable bowel syndrome. The current statements are intended to guide primary care physicians in diagnosing and managing patients with irritable bowel syndrome in Hong Kong.

PET/CT Is Complementary to Fine-Needle Aspiration Cytology in Assessment of Irradiated Neck in Head and Neck Cancers.

Background. Accurate assessment of irradiated neck in squamous cell carcinoma of the head and neck (HNSCC) is essential. Fine-needle aspiration cytology is often performed for suspicious lesions but it is limited by its low negative predictive value (NPV). We postulated that F-18 fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) can overcome this limitation by its high NPV value and allow for a more accurate assessment of irradiated neck in HNSCC. Methods. Fifty-four HNSCC patients were included for the study. They all received previous irradiation to the neck. Clinical characteristics, details of radiotherapy, PET/CT results, follow-up findings, and final histological diagnosis were analyzed. Results. The sensitivity, specificity, positive predictive value (PPV), and NPV were 95.8%, 96.7%, 95.8%, and 96.7%, respectively. Age, sex, radiation dose, interval between PET/CT and radiotherapy completion, nature of radiotherapy, and use of second course of radiotherapy were not found to affect diagnostic accuracy of PET/CT. A new algorithm for investigation of masses in irradiated neck is proposed. Conclusions. PET/CT is an effective diagnostic tool and has a complementary role to FNAC in the management of irradiated neck in head and neck cancers, particularly in cases where suspicious lesions were identified but FNAC showed negative results.

Free-flap harvesting from paralytic limbs of poliomyelitis patients--a safe and feasible option.

BACKGROUND: Many patients who had childhood poliomyelitis are still suffering from the late sequalae of the condition. Free-flap harvesting from the paralytic limbs from these patients is a logical approach for functional preservation. However, concerns have been raised regarding its safety due to its hypoplastic vascular system and potential donor site healing problems. CASE REPORT: A 53-year-old man with known childhood poliomyelitis presented with left facial sarcoma. After wide excision, the defect was reconstructed with a dual-island fasciocutaneous-free anterolateral thigh flap harvested from his paralytic limb. The pedicle and perforators were found to be no different from those in normal limbs. His recovery was smooth without complications. CONCLUSIONS: On the basis of our experience and current evidence in the literature, we believe that free-flap harvesting from the paralytic lower limb in poliomyelitis patients is a safe option that incurs no additional risk and allows maximal function preservation.

Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese.

Tyrosine hydroxylase deficiency is a rare neurotransmitter disorder affecting the rate-limiting step in catecholamine biosynthesis. There are about 40 cases reported worldwide. Here, we report the biochemical and molecular findings of eight unrelated Chinese patients with tyrosine hydroxylase deficiency. We have identified eight novel mutations with 5 missense, 2 nonsense and 1 splicing mutations in the TH gene, namely p.R153X, p.R169X, p.G294R, p.G315S, p.A385V, p.I394T, p.G408R, and c.1163+5G>C. The mutations of the TH gene in Chinese are heterogeneous.

A novel mitochondrial DNA deletion in a Chinese girl with Kearns-Sayre syndrome.

Kearns-Sayre syndrome is a rare disorder often caused by mitochondrial DNA rearrangement. The most commonly reported mitochondrial DNA deletion is 4977 bp in size spanning nucleotides 8469 and 13447. The clinical signs of Kearns-Sayre syndrome include chronic progressive external ophthalmoplegia, retinitis pigmentosa, heart block and cerebellar ataxia, as well as other heterogeneous manifestations including neuromuscular problems and endocrine disorders. Cardiac conduction defects can develop insidiously, leading to sudden death sometimes if not promptly recognised. This report focuses on the diagnosis of Kearns-Sayre syndrome in a Chinese girl who presented initially with short stature, delayed puberty, insidious onset of ptosis and later with typical features of Kearns-Sayre syndrome including complete heart block. Genetic analysis disclosed a novel 7.2 kilobases deletion in muscle tissue. Mitochondrial diseases have heterogeneous phenotypes and mutational analysis has proven to be an effective tool for confirming the diagnosis.

Hereditary spastic paraplegias.

We report a case of hereditary spastic paraplegia. This 38-year-old Chinese man has had lower limb weakness and spasticity for 10 years. He has normal cognition, no sensory deficits, ataxia or cataracts. There is a strong family history of spastic paraplegia. His paternal grandmother, great uncle, father, and elder brother all had weakness and spasticity. A genetic analysis showed that our patient was heterozygous for the mutation p.P361L in SPG4. He was diagnosed with spastic paraplegia type 4, autosomal dominant (SPG4, MIM#182601). About 40% of cases of hereditary spastic paraplegia are due to mutations in SPG4 encoding for spastin, while 10% are due to mutations in SPG3A encoding for atlastin. To date, 38 hereditary spastic paraplegia loci and 16 hereditary spastic paraplegia-related genes have been identified. Other features include sphincter disturbance and dorsal column disturbance. Our patient may be the first case of SPG4 confirmed by genetic analysis locally. We hope to raise clinicians' awareness of this disease and its possible molecular diagnosis.

Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Rehmanniae (RR) has a very long history of usage in traditional Chinese medicine and is usually one of the principal herb found in many herbal formulae used in diabetic foot ulcer. AIM OF THE STUDY: RR aqueous extract was investigated for its wound healing effects in a diabetic foot ulcer rat model and its detailed mechanism of actions. MATERIALS AND METHODS: A previously established diabetic foot ulcer rat model was used to assess the effect of RR extract on wound area reduction, tissue regeneration and angiogenesis. Carrageenan-induced inflammation rat model was used for inflammation study; and diabetic control was evaluated using a neonatal streptozotocin-induced diabetic rat model. RESULTS: In the RR treated group, a trend of reduction of the wound area was observed from days 8 to 18 and a significant difference (as compared with control group) was found on day 8. The ulcer healing effect of RR extract was further supported by better developed scars and epithelialization as well as good formation of capillaries with enhanced VEGF expression. Carrageenan-induced inflammation was also significantly alleviated with RR extract. CONCLUSIONS: Our results demonstrated for the first time that Radix Rehmanniae was effective in promoting diabetic foot ulcer healing in rats through the processes of tissue regeneration, angiogenesis and inflammation control, but not glycemia control. The present study provided scientific basis to support the traditional use of Radix Rehmanniae in diabetic foot ulcer.

The effects of diet and orlistat on body weight and lipid profiles in high risk Chinese patients with coronary artery disease, obesity and hypercholesterolemia.

BACKGROUND: Orlistat is a gastrointestinal lipase inhibitor approved for use in obesity. So far, no evidence has been reported on the use of orlistat in obese patients with coronary artery disease (CAD). AIM: To investigate the effect of orlistat on body weight and lipid profiles in obese patients with CAD and hypercholesterolemia. METHODS: Thirty non-diabetic patients with CAD, body mass index (BMI) > or = 25 kg/m(2) and low-density lipoprotein cholesterol (LDL-C) > or = 2.6 and < 4.1 mmol/L were put on diet for 12 weeks. Those still having a BMI > or = 25 kg/m(2) received orlistat 120 mg thrice daily for another 24 weeks. RESULTS: BMI was significantly reduced by 1.7% after 12 weeks of dietary treatment. The 24-week orlistat treatment resulted in further significant reduction in BMI (-2.8%) and LDL-C (-7.0%). CONCLUSION: Diet and orlistat treatment significantly reduced BMI and improved LDL-C in obese patients with CAD and hypercholesterolemia.

Radix Astragali and Radix Rehmanniae, the principal components of two antidiabetic foot ulcer herbal formulae, elicit viability-promoting effects on primary fibroblasts cultured from diabetic foot ulcer tissues.

Over 194 million people suffer from diabetes worldwide. The improper control of diabetes may result in diabetic foot ulcer or even amputation. Herbal medicine provides a means for treating diabetic foot ulcers for a large population in developing countries. The wound healing-enhancing activities of the principal herbs, Radix Astragali (RA) and Radix Rehmanniae (RR) in two clinically efficacious Chinese herbal formulae were studied in primary fibroblasts from diabetic foot ulcer patients. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that RA and RR significantly enhanced the viability of fibroblasts isolated from foot ulcers of diabetic patients, even from those with no response to insulin treatment. The results in this study indicate that fibroblast viability enhancement effects of RA and RR likely underlie the healing effects of F1 and F2 in diabetic foot ulcers.

Generation of an indestructible cyclin B1 by caspase-6-dependent cleavage during mitotic catastrophe.

Overriding the G(2) DNA damage checkpoint permits precocious entry into mitosis that ultimately leads to mitotic catastrophe. Mitotic catastrophe is manifested by an unscheduled activation of CDK1, caspase activation and apoptotic cell death. We found that although cyclin B1 was required for mitotic catastrophe, it was cleaved into a approximately 35 kDa protein by a caspase-dependent mechanism during the process. Cyclin B1 cleavage occurred after Asp123 in the motif ILVD(123) downward arrow, and mutation of this motif attenuated the cleavage. Cleavage was abolished by a pan-caspase inhibitor as well as by specific inhibitors for the effector caspase-6 and the initiator caspase-8. Cleavage created a truncated cyclin B1 lacking part of the NH(2)-terminal regulatory domain that included the destruction box sequence. Although cleavage of cyclin B1 itself was not absolutely required for mitotic catastrophe, expression of the truncated product enhanced cell death. In support of this, ectopic expression of this truncated cyclin B1 was not only sufficient to induce mitotic block and apoptosis but also enhanced mitotic catastrophe induced by ionizing radiation and caffeine. These data underscore a possible linkage between mitotic and apoptotic functions by caspase-dependent processing of mitotic activators.

In vitro antidiabetic activities of five medicinal herbs used in Chinese medicinal formulae.

Fructus Corni, Fructus Schisandrae Chinensis, Poria, Rhizoma Alismatis and Rhizoma Dioscoreae are commonly used in traditional Chinese medicine for diabetes treatment. They are also the component herbs of an antidiabetic foot ulcer formula with demonstrated clinical efficacy. Although some of these herbal extracts were previously shown to possess in vivo antidiabetic effects (i.e. lowering blood glucose levels), the underlying mechanisms remain elusive. The objective of this study is to investigate the possible antidiabetic mechanisms of these individual herbs, using a systematic study platform which includes four in vitro tissue models: glucose absorption into intestinal brush border membrane vesicles (BBMV), gluconeogenesis by rat hepatoma cell line H4IIE, glucose uptake by human skin fibroblasts cell line Hs68 and mouse adipocytes 3T3-L1. All tested herbs showed significant in vitro antidiabetic effects in at least two models. Fructus Schisandrae Chinensis, Poria, Rhizoma Alismatis and Rhizoma Dioscoreae showed significant inhibitory effects in the BBMV glucose uptake assay. All tested herbs showed significant stimulatory effects to the glucose uptake of Hs68 and 3T3-L1 cells, except Poria and Rhizoma Dioscoreae which were not effective to Hs68 and 3T3-L1 respectively. However, none of the tested herbs inhibited hepatic gluconeogenesis. In conclusion, the five herbs exhibited distinct antidiabetic mechanisms in vitro and hence our investigations provided scientific evidence to support the traditional usage of these herbs for diabetic treatment in medicinal formulae.

Factitious thyrotoxicosis and herbal dietary supplement for weight reduction.

This article describes three patients who developed factitious thyrotoxicosis, as well as other adverse effects, after taking herbal dietary supplements for weight reduction. All products were found to contain undeclared animal thyroid tissue and western pharmaceuticals causing the adverse effects. Adulteration is concealed addition of undeclared drugs, or other substances with therapeutic effects, to a health product. Consumption of such products, and the concealed components unwittingly, is obviously dangerous. Multiple adulterants in one product are often seen. Untoward adverse effect or drug interaction could occur. Overdose subsequent to poor standardization of the adulterants is another concern. Health care professionals must therefore be aware of the potential dangers posed by adulterated dietary supplements.

Formulation development of transdermal dosage forms: quantitative structure-activity relationship model for predicting activities of terpenes that enhance drug penetration through human skin.

Terpenes and terpenoids have been used as enhancers in transdermal formulations for facilitating penetration of drugs into human skin. Knowledge of the correlation between the human skin penetration effect (HSPE) and the physicochemical properties of these enhancers is important for facilitating the discovery and development of more enhancers. In this work, the HSPE of 49 terpenes and terpenoids were compared by the in vitro permeability coefficients of haloperidol (HP) through excised human skin. A first-order multiple linear regression (MLR) model was constructed to link the permeability coefficient of the drug to the lipophilicity, molecular weight, boiling point, the terpene type and the functional group of each enhancer. The Quantitative Structure-Activity Relationship (QSAR) model was derived from our data generated by using standardized experimental protocols, which include: HP in propylene glycol (PG) of 3 mg/ml as the donor solution containing 5% (w/v) of the respective terpene, the same composition and volume of receptor solution, similar human skin samples, in the same set of automated flow-through diffusion cells. The model provided a simple method to predict the enhancing effects of terpenes for drugs with physicochemical properties similar to HP. Our study suggested that an ideal terpene enhancer should possess at least one or combinations of the following properties: hydrophobic, in liquid form at room temperature, with an ester or aldehyde but not acid functional group, and is neither a triterpene nor tetraterpene. Possible mechanisms revealed by the QSAR model were discussed.