Selective laser trabeculoplasty vs. topical medications for step-up treatment in primary open angle glaucoma: comparing clinical effectiveness, quality of life and cost-effectiveness.

INTRODUCTION: The aim of this study was to investigate the clinical effectiveness, health related quality of life (HRQoL) and cost effectiveness of selective laser trabeculoplasty (SLT) compared to topical anti-glaucoma medications in step-up treatment of patients with primary open angle glaucoma (POAG). METHODS: Seventeen POAG patients with suboptimal IOP control despite pre-existing topical medications were subjected to adjunct SLT (50 applications 180 degrees) or second line medical therapy. Current medications were continued, and patients were followed up for 6 months for degree of intraocular pressure (IOP) lowering. HRQoL was assessed using Glaucoma Quality of Life 36-item (GlauQoL-36), Assessment of Quality of Life-7D (AQoL-7D) and Vision related Quality of Life (VisQoL). Costs involved were calculated and compared to the effect (IOP reduction) achieved in each arm. RESULTS: Ten patients were in the SLT group and 7 in the topical medication (MED) group. Mean baseline intraocular pressure (IOP) was 18.90±3.48mmHg in SLT group and 15.57±2.23mmHg in MED group. Mean reduction of IOP was 4.30±1.64mmHg in SLT group and 2.71±2.56 mmHg in MED group at 6 months which was not statistically significant (p=0.14) between two groups. All the HRQoL questionnaires did not show significant changes in the groups or between groups when compared baseline with 6-month post treatment (p-values ranging from 0.247 to 0.987). For every 1mmHg reduction in IOP, cost involved in MED group (RM53.61) was 165% of the cost involved in SLT group (RM32.56). DISCUSSION AND CONCLUSION: This study has shown that SLT was as effective clinically and tolerable as topical anti glaucoma medications and was possibly more cost effective in the step-up treatment of patients with POAG at 6 months follow- up.

Model systems for the study of Enterococcal colonization and infection.

Enterococcus faecalis and Enterococcus faecium are common inhabitants of the human gastrointestinal tract, as well as frequent opportunistic pathogens. Enterococci cause a range of infections including, most frequently, infections of the urinary tract, catheterized urinary tract, bloodstream, wounds and surgical sites, and heart valves in endocarditis. Enterococcal infections are often biofilm-associated, polymicrobial in nature, and resistant to antibiotics of last resort. Understanding Enterococcal mechanisms of colonization and pathogenesis are important for identifying new ways to manage and intervene with these infections. We review vertebrate and invertebrate model systems applied to study the most common E. faecalis and E. faecium infections, with emphasis on recent findings examining Enterococcal-host interactions using these models. We discuss strengths and shortcomings of each model, propose future animal models not yet applied to study mono- and polymicrobial infections involving E. faecalis and E. faecium, and comment on the significance of anti-virulence strategies derived from a fundamental understanding of host-pathogen interactions in model systems.

The impact of non-motor symptoms on the quality of life of Parkinson's disease patients: a longitudinal study.

BACKGROUND AND PURPOSE: Non-motor symptoms (NMSs) are common amongst patients with Parkinson's disease (PD); however, little is known about their influence on the health-related quality of life (QoL) over a defined follow-up period. The study was aimed to establish the impact of NMSs on the QoL of patients with PD over a 2-year follow-up period. METHOD: A total of 227 newly referred PD patients were prospectively recruited between 2013 and 2014. The Non-Motor Symptoms Scale was used to evaluate NMSs burden whilst QoL was assessed with the Parkinson's Disease Questionnaire-39 items. Motor disabilities were assessed using the Part III (motor) Unified Parkinson's Disease Rating Scale (UPDRSm). RESULTS: The mean age was 64.37 (10.18) years; 59.9% were males and a majority (89.0%) were ethnic Chinese. Almost 65% were unemployed and 84.6% had attained no more than secondary level of education. In the univariate analysis, total NMSs burden, age, gender, subsequent visit, Hoehn and Yahr staging, disease duration and UPDRSm score were individually predictive of change in the Parkinson's Disease Questionnaire Summary Index score from baseline to follow-up visit. However, in the multivariate analysis, total NMSs burden significantly predicted the QoL scores whilst motor scores did not. Specifically, NMS domains 2 (sleep/fatigue), 3 (mood/apathy) and 5 (attention/memory) were most significantly predictive of QoL change. CONCLUSION: Unlike motor disabilities, NMSs burden, in particular sleep, mood and attention, have a significant impact on the QoL of PD patients over a 2-year follow-up period.

Recalcitrant cystoid macular oedema in an eye with ischaemic central retinal vein occlusion - what's next?

We report a case of a middle-aged gentleman with recalcitrant macular oedema (RMO) secondary to ischaemic central retinal vein occlusion (CRVO). He was given six injections of intravitreal ranibizumab (anti-VEGF) monthly. However, his visual acuity (VA) deteriorated and the macular oedema worsened. He then received an intravitreal dexamethasone implant eight months post-CRVO. His VA and macular oedema improved dramatically and significantly at first follow-up and remained stable at six months after implant. This case can be a reference for those who treating recalcitrant macular oedema. It shows the effect of an intravitreal dexamathasone implant might have in a patient with RMO due to CRVO. The patient enjoyed improvement of vision, with clinical evidence of reduction in central macular thickness (CMT) and with no serious adverse events after a single injection up to six months post implant.

Comparing histopathological classification with MYCN, 1p36 and 17q status detected by fluorescence in situ hybridisation from 14 untreated primary neuroblastomas in Singapore.

INTRODUCTION: Neuroblastoma is the most common extracranial solid tumour in children, accounting for about 5.3 percent of all childhood cancers in Singapore. Several genetic abnormalities have been reported as prognostic markers, including amplification of the MYCN gene, deletion of the short arm of chromosome 1 (1p) and gain of the long arm of chromosome 17 (17q). However, the correlation between tumour histology and these genetic parameters remains to be established in our local population. METHODS: 14 untreated primary neuroblastoma tumours, diagnosed consecutively in our hospital between 2003 and 2007, were included for this study. Tumour tissues were classified histologically as favourable or unfavourable, according to the modification of World Heath Organization Classification of Tumours, by associating the degree of differentiation and mitotic-karyorrhectic index of the neuroblastoma to the age of the patient. Fluorescence in situ hybridisation analysis for MYCN, 1p status and 17q status were subsequently performed on tumour touch imprints. RESULTS: Five tumours with favourable histology were all negative for the three genetic parameters being investigated. The other nine tumours showing unfavourable histology exhibited one or more of the three genetic parameters. All MYCN amplified tumours either had additional 1p deletion and/or 17q gain. CONCLUSION: Our limited data suggests that 1p deletion and 17q gain are reliable independent parameters correlating with an unfavourable histology and poor clinical outcome. The use of 1p deletion and 17q gain studies, in addition to MYCN amplification studies, should be considered routinely in predicting prognosis in neuroblastomas.

Tissue-limited mosaicism in Pallister-Killian syndrome -- a case in point.

We report a case of Pallister-Killian syndrome in a term female infant. Antenatal ultrasound showed left diaphragmatic hernia and polyhydramnios. She was ventilated from birth and the diaphragm defect repaired on day 5. She had dysmorphic features, including median cleft palate, patchy frontotemporal alopecia, hypopigmented skin whorls, and bilateral profound sensorineural hearing loss. Fetal and postnatal karyotypes of peripheral lymphocytes were both normal, 46, XX. Subsequently, a skin fibroblast culture showed mosaic tetrasomy of isochromosome 12p both on G-banding and fluorescence in situ hybridization, consistent with Pallister-Killian syndrome. This case illustrates the importance of using the appropriate sample type for karyotype analysis with implications for prenatal and postnatal diagnosis.

Acute promyelocytic leukemia with a dicentric chromosome involving chromosomes 11, 17, and 18.

We report a case of acute promyelocytic leukemia with dicentric chromosome resulting from translocation of chromosomes 11, 17, and 18.

Highly complex chromosomal rearrangement of chromosome 9 in a case of chronic myeloid leukemia.

A 63-year-old man with chronic myeloid leukemia (CML) was found to have a new complex Philadelphia translocation. All of the bone marrow cells had a rearrangement of a five-way translocation, t(9;22;10;12;1), involving a single chromosome 9. The patient went into blast crisis two years after initial diagnosis and the karyotype remained unchanged. He died in blast crisis 10 months later. We believe this case is a unique 5-way translocation in which four chromosomes were translocated to a single chromosome.

Williams syndrome--the Singapore General Hospital experience.

Williams syndrome first described in 1961 is generally characterised by mental deficiency, gregarious personality, unusual "elfin" facies, supravalvular aortic stenosis and idiopathic infantile hypercalcaemia. Patients with Williams syndrome show a hemizygous submicroscopic deletion of 7q11.23 detectable by fluorescent in-situ hybridisation (FISH). The deleted portion of the chromosome corresponds to the Elastin gene. We report 3 girls with characteristics of Williams syndrome in whom the diagnosis was confirmed by demonstration of the hemizygous deletion of 7q11.23 in the karyotype by FISH. These patients, aged 6, 7 and 10 years, showed the characteristic facies and gregarious personalities. Some developmental delay with mild mental deficiency and dysmorphic facies were prominent features in the initial presentation. Cardiac lesions found in these patients were small patent ductus arteriosus which closed, pulmonary valvular stenosis and mitral valve prolapse associated with mitral regurgitation respectively. Hypercalcaemia was not documented in these patients. Learning difficulty was a major issue and all patients required special schooling. Chromosome analyses done on peripheral blood were found to be normal in all patients. FISH using the Elastin Williams Syndrome Chromosome Region (WSCR) probes (oncor) showed the hemizygous deletion of 7q11.23. Diagnosis of Williams syndrome can now be confidently confirmed with the help of FISH.

Partial monosomy for chromosome 22 in a girl with mental retardation.

This report describes a 5-year 6-month-old Chinese girl with partial monosomy for the long arm of chromosome 22. The karyotype was 46,XX/46,XX,del (22) (q13.2). She presented with global developmental delay. Clinical features include seizures, failure-to-thrive, prominent ears, long philtrum and abnormal skin pigmentation on the face and limbs.

Subtle translocation (18;21) confirmed by FISH in a patient with Down syndrome.

The patient presented with the typical features of Down syndrome; hypotonia, brachycephaly, flattened occiput, bilateral prominent medical epicanthic folds, flat nasal bridge, protruding tongue, low-set dysplastic ears, short broad hands, bilateral clinodactyly and simian crease. The karyotype of this child was originally reported as normal. High-resolution chromosomes revealed extra material on the long arm of chromosome 18. The mother's karyotype showed a reciprocal translocation between the long arm of 18 and the long arm of 21 at band q23 and q22.1, respectively. FISH performed separately with two different 21q cosmid probes gave two signals on the mother's metaphases and three signals on the proband. These findings confirmed that the proband is trisomic for the long arm of chromosome 21 at loci D21S65 and D21S19.

Del(3) (p25.3) without phenotypic effect.

A terminal deletion of chromosome 3 at p25.3 was observed during prenatal diagnosis. A similar deletion is also present in the phenotypically normal mother. The deletion was confirmed by FISH. The breakpoint is distal to the region responsible for the 3p- syndrome. A normal baby girl was born with no apparent phenotypic abnormalities.

Minimal sequence requirements for the regulated expression of rbcS-3A from Pisum sativum in transgenic tobacco plants.

RbcS-3A, the most highly expressed member of the pea multigene family encoding the small subunit of ribulose 1,5-bisphosphate carboxylase, is expressed in a light-dependent and organ-specific manner. In order to further delineate the sequences which mediate this complex pattern of regulation, putative regulatory sequences were assayed for function in transgenic tobacco plants in the context of an inactive 5' deleted rbcS-3A test gene. We have identified a minimal functional unit of 58 bp which is able to confer organ-specific transcriptional activity. It contains two sequences conserved among the pea rbcS family members, namely box II (-151 to -138; GTGTGGTTAATATG) and box III (-125 to -114; ATCATTTTCACT). These sequences bind the nuclear factor termed GT-1 in vitro. Substitution mutations within this 58 bp element have demonstrated that sequences upstream of, or located between, boxes II and III are not required for the transcriptional activity conferred by this element. Distance and orientation of these sequences from the gene are not critical for activity within the limits tested. DNA fragments upstream of nucleotide -170 of rbcS-3A that contain other GT-1 binding sites can also confer regulated expression upon the rbcS-3A promoter deleted to -50. Multimers of individual motifs, namely four tandem copies of boxes II and III, are unable to drive expression of the deleted promoter. These observations suggest that while GT-1 binding is necessary for promoter activity it is by itself not sufficient.

Binding site requirements for pea nuclear protein factor GT-1 correlate with sequences required for light-dependent transcriptional activation of the rbcS-3A gene.

Nuclear protein factor GT-1 binds to sequence boxes II, III, II* and III* upstream of the light-responsive pea rbcS-3A gene. We have shown previously that box II and box III are required for expression of rbcS-3A when redundant elements upstream of -170 (relative to the transcription start site) are removed. Here we present evidence that deletion and substitution mutations downstream of -170 which eliminate expression also decrease binding. Using a series of 2 bp substitution mutations we have defined a core of six residues (GGTTAA) within box II (GTGTGGTTAATATG) that are critical for binding. The most detrimental mutation for binding, which changes the double Gs to Cs, is sufficient to eliminate detectable expression in vivo when only 170 bp of 5' flanking sequences are present. The simplest interpretation of these data is that GT-1 is an activator of rbcS-3A transcription. Footprinting experiments show that GT-1 from both light-grown and dark-adapted plants binds to the same sequences in vitro. Therefore, the lack of expression of rbcS-3A in the dark is not due to the absence of GT-1. In our analysis of the sequence elements upstream of -170, we have mapped two additional GT-1 sites (boxes II** and III**) between -330 and -410. The similarities and differences among the GT-1 sites located upstream and downstream of -170 are discussed in terms of the different sequence requirements for rbcS-3A expression during development.