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The heavy metal load in coral reefs of Singapore has not been comprehensively assessed since 1994. Here, we repeated the surveys conducted 27 years ago to quantify the levels of Cd, Cu, Cr, Fe, Pb, Ti, Zn in sediment and the sea urchin Diadema setosum from seven reefs. Cu and Cd showed significant reductions, Pb and Cr remained stable, while Fe, Ti and Zn had increased significantly. Overall, based on the Pollution Load Index (PLI), Singapore's reefs would not be considered polluted. Nevertheless, elevated concentrations of Cu, Pb and Zn were detected in sediment, with Cu and Pb exceeding the Threshold Effect Level. The spatial distribution of metal loads between sediment and sea urchin tissues were decoupled, underscoring the complexity of metal uptake and bioavailability. We reveal a mixed temporal trend among the heavy metals examined, each presenting different toxicity potentials and hence risks to local marine assemblages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Given a lack of data on diabetes care performance in Malaysia, we conducted a cross-sectional study to understand the clinical characteristics, control of cardiometabolic risk factors, and patterns of use of guideline-directed medical therapy (GDMT) among patients with type 2 diabetes (T2D), who were managed at publicly-funded hospitals between December 2021 and June 2022., Methods: Patients aged ≥18 years with T2D from eight publicly-funded hospitals in the Greater Kuala Lumpur region, who had ≥2 outpatient visits within the preceding year and irrespective of treatment regimen, were eligible. The primary outcome was ≥2 treatment target attainment (defined as either HbA1c <7.0%, blood pressure [BP] <130/80 mmHg, or low-density lipoprotein cholesterol [LDL-C] <1.8 mmol/L). The secondary outcomes were the individual treatment target, a combination of all three treatment targets, and patterns of GDMT use. To assess for potential heterogeneity of study findings, all outcomes were stratified according to prespecified baseline characteristics namely 1) history of atherosclerotic cardiovascular disease (ASCVD; yes/no) and 2) clinic type (Diabetes specialist versus General medicine)., Results: Among 5094 patients (mean±SD age 59.0±13.2 years; T2D duration 14.8±9.2 years; HbA1c 8.2±1.9% (66±21 mmol/mol); BMI 29.6±6.2 kg/m2; 45.6% men), 99% were at high/very high cardiorenal risk. Attainment of ≥2 treatment targets was at 18%, being higher in General medicine than in Diabetes specialist clinics (20.8% versus 17.5%; p = 0.039). The overall statin coverage was 90%. More patients with prior ASCVD attained LDL-C <1.4 mmol/L than those without (13.5% versus 8.4%; p<0.001). Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors (13.2% versus 43.2%), glucagon-like peptide-1 receptor agonists (GLP1-RAs) (1.0% versus 6.2%), and insulin (27.7% versus 58.1%) were lower in General medicine than in Diabetes specialist clinics., Conclusions: Among high-risk patients with T2D, treatment target attainment and use of GDMT were suboptimal., Competing Interests: LLL report receiving grants through her affiliated institutions and/or honoraria for consultancy and speaker bureau from Abbott, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, Roche, Sanofi, Servier, and Zuellig Pharma. SPC report receiving the research grant through her affiliated Society (Malaysian Endocrine and Metabolic Society) and honoraria for consultancy and speaker bureau from Abbott, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Roche, Sanofi, Servier, and Zuellig Pharma. KR and PS are employee of Boehringer Ingelheim. Other co-authors declared no potential conflict of interest. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported. Six variants were novel. We analysed the clinical and genetic findings in our series and compared them with reported BFLS patients. Affected males had classic features of BFLS including intellectual disability, distinctive facies, large ears, gynaecomastia, hypogonadism and truncal obesity. Carrier female relatives of affected males were unaffected or had only mild symptoms. The phenotype of affected females with de novo variants overlapped with the males but included linear skin hyperpigmentation and a higher frequency of dental, retinal and cortical brain anomalies. Complications observed in our series included keloid scarring, digital fibromas, absent vaginal orifice, neuropathy, umbilical hernias, and talipes. Our analysis highlighted sex-specific differences in PHF6 variant types and locations. Affected males often have missense variants or small in-frame deletions while affected females tend to have truncating variants or large deletions/duplications. Missense variants were found in a minority of affected females and clustered in the highly constrained PHD2 domain of PHF6. We propose recommendations for the evaluation and management of BFLS patients. These results further delineate and extend the genetic and phenotypic spectrum of BFLS., (© 2023. The Author(s).)

Purpose: Vitamin D deficiency and insufficiency is common among populations globally, and in Asia and Malaysia. The purpose of this Position Paper is to propose recommendations for both clinicians and non-clinicians to promote vitamin D sufficiency in Malaysian adults. Formation of a national multisector, multidisciplinary alliance is also proposed to progress initiatives relating to safe sun exposure, adequate vitamin D intake through food fortification, and vitamin D supplementation for high-risk groups., Methods: Literature reviews were undertaken to inform summaries of the following: vitamin D status globally and in Asian and Malaysian populations, vitamin D status among individuals with common medical conditions, and current recommendations to achieve vitamin D sufficiency through sun exposure, food intake and supplementation. Recommendations were based on the findings of the literature reviews, recent European guidance on vitamin D supplementation, the 2018 road map for action on vitamin D in low- and middle-income countries, and research recommendations proposed by the Malaysian Ministry of Health in 2017., Results: Recommendations on assessment of vitamin D in the adult Malaysian population include using serum or plasma 25-hydroxyvitamin D concentration as a biomarker, widespread participation by Malaysian laboratories in the Vitamin D Standardization Program, adoption of the US Endocrine Society definitions of vitamin D deficiency and insufficiency, and development of a comprehensive nationwide vitamin D status study. Specific high-risk groups are identified for vitamin D assessment and recommendations relating to loading doses and ongoing management are also made., Conclusion: This Position Paper provides individual clinicians and national stakeholder organisations with clear recommendations to achieve vitamin D sufficiency in the adult population of Malaysia., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications., Methodology: A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels., Results: 113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C-peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C-peptide levels., Conclusion: Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications., Competing Interests: The authors declared no conflict of interest., (© 2023 Journal of the ASEAN Federation of Endocrine Societies.)

The global health burden of diabetes is on the rise and has affected more than half a billion people worldwide, particularly in Southeast Asia, North Africa, Africa, and the Western Pacific, Middle East, and South and Central America regions of the International Diabetes Federation (IDF). Despite many new treatments being available for the management of diabetes, glycemic control remains suboptimal in Asia, compared to the rest of the world. Delay in timely insulin initiation and inadequate titration of insulin are regarded to be some of the important reasons for inadequate glycemic control. Additionally, Asian populations have a distinct phenotype, including a younger age of onset and higher glycemic excursions, suggestive of a lower beta-cell function, as compared to non-Asians. Although there are multiple local and international guidelines on insulin initiation and titration, some of these guidelines can be complex. There is an unmet need for guideline recommendations on basal insulin initiation and titration to be simplified and customized for the Asian population with type 2 diabetes mellitus (T2DM). A unified approach would increase adoption of basal insulin initiation by primary care and family medicine physicians, which in turn would help reduce the inertia to insulin initiation. With this background, a consensus-seeking meeting was conducted with 14 experts from seven Asian countries to delineate appropriate practices for insulin initiation and titration in the Asian context. The key objective was to propose a simple insulin titration algorithm, specific for the Asian population, to improve glycemic control and optimize therapeutic outcomes of people with T2DM on basal insulin. Following a detailed review of literature and current guidelines, and potential barriers to insulin initiation and titration, the experts proposed a simplified insulin titration algorithm based on both physician- and patient-led components. The consensus recommendations of the experts related to basal insulin initiation and titration have been summarized in this article, along with the proposed titration algorithm for optimizing glycemic control in the Asian population with T2DM., (© 2022. The Author(s).)

Introduction: Prediabetes, typically defined as blood glucose levels above normal but below diabetes thresholds, denotes a risk state that confers a high chance of developing diabetes. Asians, particularly the Southeast Asian population, may have a higher genetic predisposition to diabetes and increased exposure to environmental and social risk factors. Malaysia alone was home to 3.4 million people with diabetes in 2017; the figure is estimated to reach 6.1 million by 2045. Developing strategies for early interventions to treat prediabetes and preventing the development of overt diabetes and subsequent cardiovascular and microvascular complications are therefore important., Methods: An expert panel comprising regional experts was convened in Kuala Lumpur, for a one-day meeting, to develop a document on prediabetes management in Malaysia. The expert panel comprised renowned subject-matter experts and specialists in diabetes and endocrinology, primary-care physicians, as well as academicians with relevant expertise., Results: Fifteen key clinical statements were proposed. The expert panel reached agreements on several important issues related to the management of prediabetes providing recommendations on the screening, diagnosis, lifestyle and pharmacological management of prediabetes. The expert panel also proposed changes in forthcoming clinical practice guidelines and suggested that the government should advocate early screening, detection, and intensive management of prediabetes., Conclusion: This document provides a comprehensive approach to the management of prediabetes in Malaysia in their daily activities and offer help in improving government policies and the decision-making process.

Background: Our earlier study, published in 2004,found no skin cancer in a cohort of paediatric organ transplant recipients (POTRs) 5-16 years post-transplantation. We re-evaluated the same cohort 10 years later., Objectives: To determine the prevalence of premalignant and malignant skin lesions and identify known risk factors associated with melanocytic naevi in a U.K. paediatric transplant population., Methods: Ninety-eight POTRs from the original 2004 study were invited to participate in this longitudinal follow-up study. History of sun exposure, demographics and transplantation details were collected using face-to-face interviews, questionnaires and case note reviews. Skin examination was performed for regional count of malignant lesions, benign and atypical naevi., Results: Of the 98 patients involved in the initial study, 45 POTRs (eight kidney, 37 liver), with a median follow-up of 19 years (range 15-26 years), agreed to participate. Neither skin cancer nor premalignant lesions were detected in these patients. When compared with the 2004 cohort, 41 patients in our current cohort had increased numbers of benign naevi (P < 0·001) with 11 patients having ≥ 50 benign naevi. Seventy-one per cent of benign naevi in our 2014 cohort occurred on sun-exposed sites (13% head/neck, 35% arms and 23% legs). Patients who regularly used sunscreen had more benign naevi on their arms (P = 0·008)., Conclusions: Although skin cancer was not observed in our cohort, we identified a significant increase in the number of benign naevi, particularly in those reporting frequent sunburn and sunscreen use., (© 2018 British Association of Dermatologists.)

Unlabelled: Hypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of this report is to present a case of BL presenting with panhypopituitarism and to review other case reports of lymphoma presenting with pituitary dysfunction to highlight the distinguishing features of these cases from other benign aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas. We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction published from 1998 to 2013 including the present case. The demographics, clinical presentations, laboratory features, radiological findings, histological diagnosis, treatment administered and outcomes were described. Of the total number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while 27.3% had BL. Anterior pituitary dysfunction was more common than posterior pituitary dysfunction at presentation. The other common associated presenting symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms. Hypothalamic-pituitary abnormalities were often demonstrated radiologically to be associated with cavernous sinus and/or stalk involvement. All patients who completed immunochemotherapy responded haematologically. Pituitary dysfunction also improved in most cases although the recovery tended to be partial. In conclusion, a high index of suspicion of underlying malignancy, such as lymphoma, should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, rapidly evolving neurological features, radiological features atypical of a pituitary adenoma and constitutional symptoms. An early diagnosis is essential as prompt initiation of definitive therapy will induce disease remission and recovery of pituitary dysfunction., Learning Points: Hypopituitarism may be the presenting symptom of lymphoma in the absence of associated overt symptoms or signs of a haematological malignancy resulting in delay in diagnosis and institution of treatment.Pituitary dysfunction due to tumour infiltration has a greater tendency to involve the posterior pituitary and infundibulum resulting in diabetes insipidus and hyperprolactinaemia compared with a non-functioning pituitary adenoma.The common associated symptoms of hypopituitarism due to lymphoma infiltration of the hypothalamic-pituitary system include painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms.Radiological abnormalities of the hypothalamic-pituitary region are usually present and often associated with cavernous sinus or stalk involvement.With early institution of definitive treatment, both haematological response and improvement of pituitary dysfunction are expected although the reversal of hypopituitarism tends to be partial and delayed.A high index of suspicion of underlying malignancy such as lymphoma should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, radiological features atypical of pituitary adenomas and constitutional symptoms to enable early diagnosis and prompt initiation of definitive therapy.

This is a case report of an 80-year-old woman who presented to the ENT services with multiple non-specific upper aerodigestive tract symptoms. Despite extensive investigation and treatment, her symptoms remained unalleviated with significant impact on the psychological morbidity. During a routine flexible nasoendoscopy for worsening globus pharnygis, a mass was noted in the right Rosenmüller's fossa, where the Eustachian tube leaves the lateral wall of the nasopharynx. A CT scan showed this to be a 10 mm calcified entity within the right Eustachian tube. It was subsequently removed under local anaesthesia providing much relief to the patient. Histology showed this mass to be a rhinolith.

In most eukaryotes, the HISTONE 3 family comprises several variants distinguished by their amino acid sequence, localization, and correlation with transcriptional activity. Transgenerational inheritance of epigenetic information carried by histones is still unclear. In addition to covalent histone modifications, the mosaic distribution of H3 variants onto chromatin has been proposed to provide a new level of epigenetic information. To study the transmission of patterns of H3 variants through generations, we combined transcriptional profiling and live imaging of the 13 H3 variants encoded by the Arabidopsis plant genome. In comparison with somatic cells, only a restricted number of H3 variants are present in male and female gametes. Upon fertilization, H3 variants contributed by both gametes are actively removed from the zygote chromatin. The somatic H3 composition is restored in the embryo by de novo synthesis of H3 variants. A survey of Arabidopsis homologs of animal H3 chaperones suggests that removal of parental H3 from the zygote nucleus relies on a new mechanism. Our results suggest that reprogramming of parental genomes in the zygote limits the inheritance of epigenetic information carried by H3 variants across generations., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Pyrosequencing is a DNA sequencing technique based on sequencing-by-synthesis enabling rapid and real-time sequence determination. Although ample genomic research has been undertaken using pyrosequencing, the requirement of relatively high amount of DNA template and the difficulty in sequencing the homopolymeric regions limit its key advantages in the applications directing towards clinical research. In this study, we demonstrate that pyrosequencing on homopolymeric regions with 10 identical nucleotides can be successfully performed with optimal amount of DNA (0.3125-5 pmol) immobilized on conventional non-porous Sepharose beads. We also validate that by using porous silica beads, the sequencing signal increased 3.5-folds as compared to that produced from same amount of DNA immobilized on solid Sepharose beads. Our results strongly indicate that with optimized quantity of DNA and suitable solid support, the performance of pyrosequencing on homopolymeric regions and its detection limit has been significantly improved., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Most functional phaeochromocytomas/paragangliomas produce noradrenaline and/or adrenaline. Those that produce dopamine are rare. We describe the distinguishing clinical features of dopamine-secreting phaeochromocytomas and paragangliomas from those that secrete noradrenaline/adrenaline and the impact on their management. We present a case of a dopamine-secreting paraganglioma from our institution and review 14 case reports of dopamine-secreting phaeochromocytomas/paragangliomas published between 1984 and 2008. As observed in the literature, 80% of the tumours were extra-adrenal. Most patients presented with non-specific symptoms or mass effect without the classical presentation of catecholamine excess. The majority were diagnosed with urinary or plasma dopamine. Five patients had malignant tumours and 12 patients underwent surgical resection of the primary tumours. Unlike noradrenaline/adrenaline-secreting phaeochromocytomas/paragangliomas, dopamine-secreting tumours lack a classical presentation, are extra-adrenal and have a higher malignant potential. A routine inclusion of urinary or plasma dopamine as part of catecholamine screening in all suspected phaeochromocytomas and paragangliomas is recommended.

Investigation of a microbial fermentation organic extract of Streptomyces sp. H7667 led to the isolation of three new imides, 3-[(5E)-5-methyl-4-oxo-2-hydroxy-5-octenyl]glutarimide (1), 2-amino-N-2'-(phenylacetyl)propanimide (5), and 2-amino-N-(2'-(cyclohex-2''-enyl)acetyl)acetimide (6), and one new isoflavonoid glycoside, 6-O-methyl-7-O-alpha-rhamnopyranosyldaidzein (7), along with four known compounds. Their structures were elucidated by HRESIMS, 1H and 13C NMR, COSY, HMQC, HMBC, and NOESY spectra. Compounds 1-8 were evaluated for their inhibitory activities in the yeast glycogen synthase kinase-3beta assay.

Background: Little is known of risk factors for stroke among Chinese immigrants to the United States. We have conducted a case-control study to identify risk factors for stroke among foreign-born Chinese in New York City., Methods: From September 2000 to June 2003, 187 sequential stroke cases (44 hemorrhagic) and 204 controls matched on age, gender, and years since immigration were recruited from New York Downtown Hospital, which was located next to New York City Chinatown. Risk factor status was assessed by questionnaire interview and medical chart review, which included clinical factors, sociodemographic characteristics, personal and family histories, and behavior and lifestyle factors, as well as behavioral changes after immigration to the United States., Results: For cases and controls, mean ages were 74.8 and 74.7 years, 47.3% of cases and 47.5% of controls were male, and mean years since immigration to the United States were 26.7 and 26.8, respectively. Sociodemographic characteristics and behavioral pattern including cigarette smoking, exercise, and usage of special diet or dietary supplements were similar between cases and controls. However, stroke patients were more likely to have hypertension (76% vs. 59%, p

Background: Limited information exists on clinical characteristics of stroke among Chinese persons living in the United States. We compared the clinical characteristics of Chinese and White stroke patients living in New York City., Methods: We reviewed the medical records of stroke patients hospitalized at NYU Downtown Hospital from January 1995 to July 1998., Results: During 3.5 years, there were 728 admissions for stroke (454 Chinese, 115 Whites, 75 Blacks, 80 Hispanics, and 4 other Asia). Chinese and White patients had similar age and gender distributions. Compared with Whites, Chinese patients had a lower body mass index (22.8 vs 25.8, respectively, P=0.02), were less likely to smoke (13% vs 20%, respectively, P<0.01), or regularly consume alcohol (8% vs 25%, respectively, P<0.01). Although recorded blood pressure was similar, Chinese patients were more likely than Whites to have a history of hypertension (77% vs 64%, respectively, P=0.03), left ventricular hypertrophy (37% vs 25%, respectively. P=0.02), history of diabetes (33% vs 21%, respectively, P=0.01), and higher levels of blood lipids and glucose. Chinese patients were more likely than Whites to have hemorrhagic stroke (24% vs 17%, respectively, P=0.02). Overall age-adjusted in-hospital mortality rate was 14.2%, and no significant difference was observed between Chinese and Whites (13.8% vs 14.8%, respectively, P=0.1). For both races, hemorrhagic stroke was far more likely to be fatal than ischemic stroke (34.5% vs 6.1%, respectively, P<0.001). Factors associated with in-hospital death included systolic blood pressure, blood glucose level, history of coronary heart disease, and diabetes., Conclusions: Chinese patients who suffered a stroke showed higher risk profiles, and were more likely to experience a more lethal hemorrhagic stroke, compared to White patients. The short-term in-hospital survival rates were similar between Chinese and White patients with stroke.

Purpose: The interactive effects of synthetic polyaramid reinforcement fibers on the transverse strength of intact and repaired heat-polymerized denture base acrylic resins were investigated., Materials and Methods: Three polymethylmethacrylate (PMMA) polymers were tested: Acron MC (GC International Corp, Scottsdale, AZ), Lucitone 199 (Dentsply International Inc, York, PA), and Microlon (The Hygienic Corp, Akron, OH). With each polymer, there were 2 controls and 4 experimental groups (n = 9 per group). The treatment groups were intact heat-polymerized PMMA control, PMMA with unreinforced repair, PMMA with polyaramid reinforced repair, intact polyaramid reinforced heat-polymerized PMMA control, polyaramid reinforced PMMA with unreinforced repair, and polyaramid reinforced PMMA with polyaramid reinforced repair. The transverse fracture strengths of the samples were measured with a 3-point bending test on a Zwick Universal Testing Machine (Zwick of America, Inc, East Windsor, CT)., Results: The highest mean strength at fracture was recorded with intact polyaramid reinforced heat-polymerized PMMA controls for all resins. Analysis of variance showed significant differences in transverse strength (p < .05) by experimental group, by material, and by interaction of group and material. Tukey HSD (honestly significant difference) Multiple Comparisons Test (alpha = 0.05) showed that intact polyaramid reinforced heat-polymerized PMMA controls were significantly stronger than intact heat-polymerized PMMA controls and all the other treatment groups. Use of polyaramid reinforcement in repair of unreinforced PMMA or polyaramid reinforced PMMA did not result in significantly increased transverse strength., Conclusions: Polyaramid reinforcement significantly increased the transverse strength of intact heat-polymerized PMMA. Polyaramid fibers did not significantly increase strength to reinforce PMMA repairs., (Copyright 2001 by The American College of Prosthodontists.)

Over a 30-month period from July 1995 to December 1997, new detections of methicillin-resistant Staphylococcus aureus (MRSA) were prospectively studied in a tertiary referral hospital. The aims of the study were to determine the incidence of colonization of patients admitted to each of the hospital's 39 clinical units and ascertain where each patient had become colonized. Epidemiological information (time to detection, ward movement, admission to other hospitals, data on MRSA isolations in hospital wards) and phage typing were used by the hospital's infection control unit to make this determination. Routine containment procedures included cohorting, flagging and triclosan body washes. Surveillance cultures were collected infrequently. Patients known to be colonized with MRSA were excluded from orthopaedic and haematology wards. During the study period, 995 patients were found to be newly colonized. The incidence of colonization varied from nil to 72 per 1000 admissions, being highest in the main intensive care unit and in services which frequently used that unit. The incidence of colonization in elective orthopaedic surgery (< 1 per 1000) and haematology (3 per 1000) was very low. Determining the place where patients acquired MRSA was made difficult by the high frequency of endemic phage types and frequent patient transfer between wards. Epidemiological data suggested that the main intensive care unit and surgical wards nursing patients with colorectal, urological and vascular diseases were the places where most patients became colonized. MRSA was never acquired by patients nursed in wards which practised an exclusion policy towards patients known to be colonized with MRSA. Our data suggest that in tertiary referral hospitals, where MRSA is not only endemic but frequently imported from other hospitals, it is possible to establish areas where MRSA is never acquired., (Copyright 2000 The Hospital Infection Society.)

The aim of this study was to compare the amounts and pattern of fluoride release and antibacterial properties of new-generation restoratives over a 35-day period. Materials evaluated included fluoride-releasing composites (Tetric, Experimental X), compomers (Dyract, Compoglass), and a resin-modified glass-ionomer cement (Fuji II LC). A conventional glass ionomer (Fuji II Cap) was used as a control for fluoride-release testing. Five samples of each restorative material were evaluated for daily fluoride release over a 35-day period by means of ion chromatography. Ranking of materials from least to greatest total fluoride release over 35 days was as follows: Tetric < Experimental X < Dyract < Fuji II LC < Compoglass < Fuji II Cap. Fuji II Cap had significantly greater fluoride release than all other materials evaluated. Fuji II Cap, Fuji II LC, and Compoglass had similar patterns of fluoride release characterized by a high initial release that was many times that released later. The fluoride-releasing composites evaluated stopped releasing fluoride by day 14. Antibacterial testing was conducted using the agar diffusion inhibitory test. Five samples of each restorative were assessed at baseline and weekly intervals up to 35 days. The microorganisms used were Lactobacillus casei, Streptococcus mutans, and Streptococcus sobrinus. IRM, a zinc oxide/eugenol cement, was used as the baseline control. None of the restorative materials evaluated affected the growth of L casei, S sobrinus, or S mutans at all time periods including baseline, where fluoride was detected in the agar beneath the specimen disks. There was no correlation noted between fluoride-release potential and antibacterial properties.

Measurements of hippocampal formation atrophy using MRI have been useful in distinguishing demented patients with a diagnosis of probable Alzheimer's disease from cognitively normal controls. To determine whether there is a similar relationship between hippocampal size and dementia in elderly patients suspected of normal pressure hydrocephalus (NPH), the authors obtained mini-mental status examination (MMSE) scores and MRI measurements of hippocampal size and CSF volume on 16 elderly patients whose severe ventriculomegaly and unexplained gait impairment made NPH a probable diagnosis. Hippocampal size correlated strongly with MMSE score (r = 0.75, p < 0.001); no significant MMSE correlation was found for ventricular CSF volume or extra-ventricular/ventricular CSF ratio. It was concluded that hippocampal atrophy is associated with severe cognitive dysfunction in many elderly patients with a diagnosis of NPH. As a hypothesis for further investigation, the detection of such atrophy may help identify cases where the presence of a pathology of Alzheimer's disease complicates the diagnosis of NPH.

Five patients with hydrocephalus were studied with carbon-11-2-deoxyglucose or 2-deoxy-2-(18F) fluoro-D-glucose and positron emission tomography both prior to and following ventricular shunting. Four subjects had communicating hydrocephalus; the fifth had aqueductal stenosis, two patients had hydrocephalus for three months or less. The three chronic patients were felt to have hydrocephalus for three years or more. After shunting ventricular size decreased in all patients, and all patients showed clinical improvement. The glucose cerebral metabolic rates increased after shunt in the two subjects with recent onset hydrocephalus but paradoxially decreased in the three chronic patients despite clinical improvement. These findings suggest that the cerebrum was metabolically hyperactive prior to shunt due to an unknown mechanism and presumably in response to the presence of hydrocephalus. A dissociation may also exist in the post-shunt period between cerebral metabolism and cerebral blood flow.

We treated five patients with 11 supraophthalmic infusions of BCNU at 200 mg/m2 every 2 months. All three patients with residual tumors showed marked CT response after one infusion. Two patients with bilateral tumors had no response on the contralateral side. All four evaluable cases showed evidence of BCNU neurotoxicity. CT findings superficially resembled tumor recurrence, but white matter changes, nonspecific gyral enhancement, and delayed calcification were more indicative of neurotoxicity. There were no procedure-related complications. One autopsy suggested that direct parenchymal damage might be responsible for delayed neurotoxicity. Supraophthalmic BCNU infusion, at this dosage, is too toxic for cerebral tissue.

Bromocriptine and lergotrile were administered to 81 patients with Parkinson disease (PD) and increasing disability despite optimal treatment with levodopa (secondary levodopa failures). Sixty-six patients were treated with bromocriptine and 53 patients were treated with lergotrile. Both groups had significantly decreased rigidity, tremor, bradykinesia and gait disturbance upon addition of bromocriptine or lergotrile to levodopa. Twenty-five patients improved at least one-stage on bromocriptine, and 21 improved at least one-stage on lergotrile. The mean dose of bromocriptine was 47 mg, and the mean dose of lergotrile was 49 mg, permitting a 10% reduction in levodopa. Bromocriptine was discontinued in 29 of 66 patients because of adverse effects, including mental changes (14 patients) and involuntary movements (9 patients). Lergotrile was discontinued in 33 of 53 patients because of adverse effects including hepatotoxicity (11 patients) and mental changes (12 patients). The results of treatment with bromocriptine or lergotrile were comparable, with patients either responding or not. Bromocriptine will shortly be available for use in PD. Lergotrile, because of the hepatotoxicity, will not.

We studied the effects of intra-arterial chemotherapy on the visual system of 29 consecutive patients with gliomas. As expected, infra-ophthalmic carotid infusion of cisplatin or carmustine (BCNU) was associated with clinically apparent anterior visual pathway lesions. Electroretinography revealed retinal dysfunction in patients without clinical abnormalities. Supra-ophthalmic carotid infusion of cisplatin or BCNU caused no retinal or optic nerve lesions. Electroretinography was abnormal in only one of these patients. Our results indicated that BCNU and cisplatin cause ischemic damage and are toxic to both retinal and neural tissue in patients with gliomas.

We reviewed the serial CT studies obtained between 1974 and 1986 of 31 patients with malignant glioma who survived for 2 to 11 years after surgical removal of their tumors. In all cases surgery was followed by radiation therapy to the head (6000 rad) and chemotherapy. Patients were divided into two age groups: those under age 40 (n = 13) and those over age 40 (n = 18). By 2 years all patients in the older group developed evidence of leukoencephalopathy characterized by periventricular zones of decreased attenuation. Only 58% of the younger group showed evidence of white matter changes at this point. All patients from both age groups who survived for 4 years developed leukoencephalopathy. The severity of leukoencephalopathy from 6 months after surgery and beyond was always greater in the older group. All patients developed cerebral atrophy as evidenced by sulcal dilatation and ventricular enlargement. Atrophy was progressive beginning with the first postirradiation scan, and was always more severe in the older patients. A significant difference was found in the clinical status of the two age groups as determined by the mental status score and the Karnofsky scale. Despite progressive brain changes, survivors under age 40 maintained a nearly normal mental status and Karnofsky scores until their death, whereas survivors over age 40 showed progressive clinical decline.

The serial pre- and postoperative computed tomographic (CT) scans of 115 patients entered in the Cooperative Brain Tumor Study between 1975 and 1982 were analyzed in order to define CT prognostic criteria and to test the hypothesis that radical glioma surgery prolongs patient survival. The CT parameters of mass size, associated edema, and intensity of enhancement were quantitated on all scans. Clinical parameters evaluated included gender, age, length of survival, and useful (Karnofsky greater than 30) survival. Data analyses indicated postoperative residual tumor burden was inversely related to length of survival (p less than 0.01). Postoperative associated edema and intensity of image enhancement were also of prognostic value and showed an inverse relation to survival. Younger patients proved more likely than older patients to attain long-term survival. Residual tumor burden of less than 45 mm diameter on postoperative CT scans was associated with 70% chance of long-term survival. These findings support the radical surgical management of glioma.

Cutaneous hyperpigmentation resembling acanthosis nigricans developed in two patients with malignant brain tumors following chemotherapy with triazinate (Baker's Antifol), a folic acid antagonist. In both cases, the eruption resolved after the cessation of drug administration and reappeared after the reinstitution of triazinate therapy. A skin biopsy specimen from one patient showed microscopic changes consistent with those found in acanthosis nigricans. The other patient had a decreased serum folate level that returned to normal as the hyperpigmentation resolved. Folate may have a role in triazinate-induced acanthosislike hyperpigmentation.

Eight of 57 patients (14%) with malignant astrocytomas lived at least 2 years. The mean survival time was 143 weeks (range, 104 to 250 weeks). All of the patients were treated with operation, radiation, and chemotherapy. Four of the 8 patients died because of tumor recurrence, 1 died from a second primary tumor, 2 died of cases unrelated to the tumor, and 1 is still alive. Diffuse cortical dysfunction associated with cortical atrophy that could not be related to tumor regrowth and was not explained by focal deficits, psychotic of depressive thought disorders, metabolic or endocrine abnormalities, or hydrocephalus developed in the 3 longest-surviving patients. The diffuse dysfunction was initially apparent only through psychometric testing, but eventually became so disabling as to result in 2 of the 3 patients retiring from work. Although small, but gratifying, gains have been made in the treatment of patients with malignant brain tumors, accompanying these gains have been problems of a magnitude that is only now beginning to be appreciated.

Twenty-eight patients with Parkinson disease (PD) were treated with bromocriptine for at least 2 years (mean, 2.8 years; range, 2 to 5 years). All of them had first been treated with levodopa (alone or combined with carbidopa, as Sinemet) for 7.4 years (range, 1 to 10 years). At the time bromocriptine was started, all were showing increasing disability. In these patients, attempts to increase levodopa resulted in adverse effects, and attempts to decrease levodopa resulted in increased parkinsonism. Bromocriptine (mean daily dose, 56 mg) was added to levodopa and resulted in improvement of at least one stage (Hoehn and Yahr scale) in 21 of the patients. After 2 years, five of these patients continue to maintain this improvement. The remaining patients, although there has been deterioration, maintain some of their original improvement. Bromocriptine, when added to levodopa, results in improvement that is maintained, in part, for at least 2 years. The ratio of bromocriptine to levodopa has to be periodically readjusted.

Deprenyl, a selective inhibitor of monoamine oxidase, type B, which is free of the "tyramine effect," may ameliorate symptom fluctuations in advanced Parkinson's disease (PD). We randomized 96 patients with marked symptom fluctuations at three centers to receive either deprenyl 5 mg b.i.d. or placebo in parallel fashion in addition to a previously optimized levodopa/carbidopa (Sinemet) regimen. Disability was recorded hourly at home by patients 3 days weekly during the 2-week baseline and the 6-week treatment period. Disability during the "on" state was assessed each week by examination. Mean hourly self-assessment of gait improved in 28 of 50 patients (56%) receiving deprenyl (mean degree of improvement 0.25 points on a 0-2 scale) and in 14 of 46 (30.4%) taking placebo (mean 0.15). Mean hourly overall symptom control improved in 29 (58%) taking deprenyl (mean 0.34) and in 12 (26.1%) taking placebo (mean 0.15) (p less than 0.01 for each parameter). No significant improvement occurred in the objective quality of the "on" state with deprenyl. Mean daily Sinemet dosage decreases were 17% in the deprenyl group and 7% in the placebo group. Adverse effects included nausea, light-headedness, dyskinesias, and hallucinations, all of which abated after the Sinemet dose was reduced. We conclude that deprenyl is of moderate benefit in a majority of patients with symptom fluctuations complicating PD and is generally well tolerated.