Animals ; Epilepsy ; genetics ; Gene Expression Regulation ; drug effects ; Glial Fibrillary Acidic Protein ; genetics ; metabolism ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology

Drug hypersensitivity syndrome (DHS) is an idiosyncratic systemic reaction to a drug. The clinical presentation of this syndrome comprises a diverse spectrum, ranging from mild to fulminating organ failure. Nonspecific gastrointestinal symptoms are common in DHS, but severe morbidities and mortalities attributed to gut disease in DHS are rarely described. We present a case of DHS with significant gastrointestinal symptoms of prolonged profuse watery diarrhoea and persistent hypokalaemia requiring judicious intravenous water and electrolyte replacement. The symptoms resolved only after the introduction of intravenous hydrocortisone. It is important to consider intravenous corticosteroids if the gastrointestinal system is involved, as accelerated gut motility and mucosal damage would affect absorption of oral medications. Supportive treatment with the monitoring of fluid and electrolytes status and judicious replacement remains fundamental in the management of DHS patients with gut involvement.
Amoxicillin-Potassium Clavulanate Combination ; therapeutic use ; Diarrhea ; complications ; diagnosis ; Drug Eruptions ; diagnosis ; drug therapy ; Drug Hypersensitivity Syndrome ; complications ; diagnosis ; Edema ; chemically induced ; Electrolytes ; Female ; Gastrointestinal Diseases ; chemically induced ; complications ; Humans ; Hydrocortisone ; therapeutic use ; Middle Aged ; Otitis Media ; complications ; drug therapy ; Prednisolone ; therapeutic use ; Stomatitis ; chemically induced

INTRODUCTIONRecognising and appropriately treating psychosomatic factors in dermatological conditions can have a significant positive impact on the outcomes of patients. Treatment of psychodermatological patients requires a multidisciplinary approach that involves dermatologists, psychiatrists and allied health professionals.

METHODSThis was a retrospective case series of patients seen in our psychodermatology liaison conferences from November 2009 to July 2011. We reviewed all the case notes and analysed data such as age, gender, dermatologic and psychiatric diagnoses, treatment and outcome.

RESULTSThe majority of patients in our cohort were diagnosed with either a psychophysiologic disorder or a primary psychiatric disorder. The most common diagnosis among patients with primary psychiatric disorder was delusions of parasitosis. Other common primary psychiatric disorders seen were trichotillomania and dermatitis artefacta. About a fifth of our patients had psychiatric disorders resulting from their underlying dermatological conditions. A third of our patients were lost to follow-up.

CONCLUSIONManaging patients with psychocutaneous disorders can be challenging, with many patients defaulting treatments. Psychodermatology clinics will benefit both patients and their caregivers. A collaborative approach using a consultation-liaison relationship between two medical departments in a friendly environment would result in more effective, integrated and holistic treatment strategies for such patients. Further studies should be conducted to determine how beneficial such services are to patients. With more experience, we hope to improve this service.

Adolescent ; Adult ; Aged ; Disease Management ; Female ; Hospitals, Special ; Humans ; Male ; Middle Aged ; Psychophysiologic Disorders ; complications ; epidemiology ; therapy ; Retrospective Studies ; Singapore ; epidemiology ; Skin Diseases ; complications ; epidemiology ; therapy ; Young Adult

Objective: Dysregulation of gene expression through epigenetic mechanisms may have a vital role in the pathogenesis of schizophrenia (SZ). In this study, we investigated the association of altered methylation patterns with SZ symptoms and early trauma in patients and healthy controls. Methods: The present study was conducted to identify methylation changes in CpG sites in peripheral blood associated with recent-onset (RO) psychosis using methylome-wide analysis. Lifestyle factors, such as smoking, alcohol, exercise, and diet, were controlled. Results: We identified 2,912 differentially methylated CpG sites in patients with RO psychosis compared to controls. Most of the genes associated with the top 20 differentially methylated sites had not been reported in previous methylation studies and were involved in apoptosis, autophagy, axonal growth, neuroinflammation, protein folding, etc. The top 15 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways included the oxytocin signaling pathway, long-term depression pathway, axon guidance, endometrial cancer, long-term potentiation, mitogen-activated protein kinase signaling pathway, and glutamatergic pathway, among others. In the patient group, significant associations of novel methylated genes with early trauma and psychopathology were observed. Conclusion Our results suggest an association of differential DNA methylation with the pathophysiology of psychosis and early trauma. Blood DNA methylation signatures show promise as biomarkers of future psychosis.

INTRODUCTIONHypertension is a common chronic condition usually managed by primary-care practitioners in Singapore. This study assessed the characteristics, control and complications of non-diabetic hypertensive patients managed at government primary healthcare clinics.

MATERIALS AND METHODSA cross-sectional study involving 9 clinics was conducted over 1-week in 2006. Five hundred and six non-diabetic hypertensive patients were systematically sampled from all clinic attendees. Data relating to socio-demographic, lifestyle factors, treatment and complications were collected by interviewer-administered questionnaires and review of clinic medical records. Blood pressure (BP) measurements were taken with validated automated sets following a standard protocol.

RESULTSThe prevalence of good BP control (<140/90 mmHg) was 37.7% (95% CI: 33.6% to 41.8%). Ninety seven percent were on medication with about half on monotherapy. Seventy percent of patients had a body mass index (BMI) of 23.0 kg/m(2) or higher, 64% did not exercise regularly and 8% were current smokers. After adjusting for age and lifestyle factors, male hypertensive patients had poorer BP control compared to females. Nineteen percent of patients reported at least 1 complication of hypertension, especially cardiac disease. After multivariate analysis and duration of disease, age and the male gender were associated with the presence of hypertensive complications.

CONCLUSIONSMore than half of the patients were not controlled to target levels. Male patients were more likely to have poorer control of hypertension and significantly higher risks of complications. Control of BP could be further improved by lifestyle modifications - weight reduction, promotion of physical activity, healthier eating habits and smoking cessation.

Aged ; Blood Pressure ; Body Mass Index ; Community-Based Participatory Research ; Confidence Intervals ; Cross-Sectional Studies ; Diet, Reducing ; Female ; Humans ; Hypertension ; complications ; diagnosis ; epidemiology ; prevention & control ; Life Style ; Male ; Middle Aged ; Motor Activity ; Multivariate Analysis ; Prevalence ; Primary Health Care ; statistics & numerical data ; Risk ; Sex Factors ; Singapore ; epidemiology ; Surveys and Questionnaires ; Weight Loss

BACKGROUNDVon Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.

METHODSNine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).

RESULTSThe nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.

CONCLUSIONSGenetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.

Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis* ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Protein-Tyrosine Kinases* ; RNA, Small Interfering ; Triple Negative Breast Neoplasms* ; Tyrosine*