Publications by authors named "K Nadira De Abrew"

26 Publications

  • Page 1 of 1

FutureTox IV Workshop Summary: Predictive Toxicology for Healthy Children.

Toxicol Sci 2021 Apr;180(2):198-211

U.S. Environmental Protection Agency, ORD, Research Triangle Park, North Carolina, USA.

FutureTox IV, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2018. Building upon FutureTox I, II, and III, this conference focused on the latest science and technology for in vitro profiling and in silico modeling as it relates to predictive developmental and reproductive toxicity (DART). Publicly available high-throughput screening data sets are now available for broad in vitro profiling of bioactivities across large inventories of chemicals. Coupling this vast amount of mechanistic data with a deeper understanding of molecular embryology and post-natal development lays the groundwork for using new approach methodologies (NAMs) to evaluate chemical toxicity, drug efficacy, and safety assessment for embryo-fetal development. NAM is a term recently adopted in reference to any technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment to avoid the use of intact animals (U.S. Environmental Protection Agency [EPA], Strategic plan to promote the development and implementation of alternative test methods within the tsca program, 2018, https://www.epa.gov/sites/production/files/2018-06/documents/epa_alt_strat_plan_6-20-18_clean_final.pdf). There are challenges to implementing NAMs to evaluate chemicals for developmental toxicity compared with adult toxicity. This forum article reviews the 2018 workshop activities, highlighting challenges and opportunities for applying NAMs for adverse pregnancy outcomes (eg, preterm labor, malformations, low birth weight) as well as disorders manifesting postnatally (eg, neurodevelopmental impairment, breast cancer, cardiovascular disease, fertility). DART is an important concern for different regulatory statutes and test guidelines. Leveraging advancements in such approaches and the accompanying efficiencies to detecting potential hazards to human development are the unifying concepts toward implementing NAMs in DART testing. Although use of NAMs for higher level regulatory decision making is still on the horizon, the conference highlighted novel testing platforms and computational models that cover multiple levels of biological organization, with the unique temporal dynamics of embryonic development, and novel approaches for estimating toxicokinetic parameters essential in supporting in vitro to in vivo extrapolation.
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http://dx.doi.org/10.1093/toxsci/kfab013DOI Listing
April 2021

A comparison of classical and 21st century genotoxicity tools: A proof of concept study of 18 chemicals comparing in vitro micronucleus, ToxTracker and genomics-based methods (TGx-DDI, whole genome clustering and connectivity mapping).

Environ Mol Mutagen 2021 02 7;62(2):92-107. Epub 2020 Dec 7.

Global Product Stewardship, The Procter & Gamble Company, Cincinnati, Ohio, USA.

A key step in the risk assessment process of a substance is the assessment of its genotoxic potential. Irrespective of the industry involved, current approaches rely on combinations of two or three in vitro tests and while highly sensitive, their specificity is thought to be limited. A refined in vitro genotoxicity testing strategy with improved predictive capacity would be beneficial and "3R" friendly as it helps to avoid unnecessary in vivo follow-up testing. Here, we describe a proof of concept study evaluating a balanced set of compounds that have in vivo negative or positive outcomes, but variable in vitro data, to determine if we could differentiate between direct and indirect acting genotoxicants. Compounds were examined in TK6 cells using an approach in which the same sample was used to evaluate both early genomic markers (Affymetrix analysis 4 hr post treatment), and the genotoxic outcome (micronuclei [MN] after 24 hr). The resulting genomic data was then analyzed using the TGx-DDI biomarker, Connectivity mapping and whole genome clustering. Chemicals were also tested in the ToxTracker assay, which uses six different biomarker genes. None of the methods correctly differentiated all direct from indirect acting genotoxicants when used alone, however, the ToxTracker assay, TGx-DDI biomarker and whole genome approaches provided high predictive capacity when used in combination with the MN assay (1/18, 2/18, 1/18 missed calls). Ultimately, a "fit for purpose" combination will depend on the specific tools available to the end user, as well as considerations of the unique benefits of the individual assays.
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http://dx.doi.org/10.1002/em.22418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898312PMC
February 2021

Assessment of distance from skin surface to muscle for evaluation of the risk of inadvertent intramuscular insulin injection at potential injection sites among patients attending a tertiary care children's hospital in Sri Lanka-an observational study.

Arch Pediatr 2020 Jul 24;27(5):244-249. Epub 2020 May 24.

Department of Pharmacology and Pharmacy, Faculty of Medicine, University of Colombo, Sri Lanka.

Background: Insulin therapy is essential for type 1 diabetes. While a reasonable glycemic control prevents complications, inadvertent intramuscular (IM) insulin injection results in hypoglycemia and fluctuations of blood glucose levels.

Objective: To assess the subcutaneous thickness (SCt) at the potential insulin injection sites, in order to determine the suitable needle length.

Methods: Diabetic and non-diabetic children (n=125; aged 2-14 years) attending a tertiary care hospital were examined, after excluding those who had skin abnormality at the injection site, were hospitalized for>3 days, or had any other chronic illnesses. Dermal thickness (Dt) and SCt at the potential insulin injection sites were measured with ultrasonography.

Results: The mean age of the patients was 8 years and 57% were boys; mean Dt was 2.1±0.4 mm, SCt was 7.45.6±3.7 mm, and maximum SCt was 29.8 mm in the anterior abdominal wall. SCt increased with age and by raising a skin fold (sf). There was no difference (P>0.05) in Dt between genders, and limbs showed thinner Dt values than the abdomen. SCt changed with the injection site: it was the lowest in the thigh and the highest in the abdomen. SCt was thicker in females, with or without sf (P<0.001). For all sites, IM risk was high for 15-mm needles: it was highest in the thighs (98%) and reduced to 86% with sf. IM risk was low for 5-mm needles: it was highest in the thigh (38%), and reduced to 12% with sf. Compared with girls (up to 42%), IM risk was higher for boys (up to 54%), even for 5-mm needles with a sf.

Conclusion: Using a short needle is recommended for children, particularly for boys. Regardless of the needle length, the raised sf technique is associated with reduced IM risk.
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http://dx.doi.org/10.1016/j.arcped.2020.05.008DOI Listing
July 2020

DPACE-based chemotherapy in the era of myeloma novel agents: A UK multicentre study.

Eur J Haematol 2020 Aug 21;105(2):231-233. Epub 2020 Apr 21.

Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

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http://dx.doi.org/10.1111/ejh.13422DOI Listing
August 2020

Use of connectivity mapping to support read across: A deeper dive using data from 186 chemicals, 19 cell lines and 2 case studies.

Toxicology 2019 07 21;423:84-94. Epub 2019 May 21.

Mason Business Center, The Procter & Gamble Company, Cincinnati, OH, 45040, USA.

We previously demonstrated that the Connectivity Map (CMap) (Lamb et al., 2006) concept can be successfully applied to a predictive toxicology paradigm to generate meaningful MoA-based connections between chemicals (De Abrew et al., 2016). Here we expand both the chemical and biological (cell lines) domain for the method and demonstrate two applications, both in the area of read across. In the first application we demonstrate CMap's utility as a tool for testing biological relevance of source chemicals (analogs) during a chemistry led read across exercise. In the second application we demonstrate how CMap can be used to identify functionally relevant source chemicals (analogs) for a structure of interest (SOI)/target chemical with minimal knowledge of chemical structure. Finally, we highlight four factors: promiscuity of chemical, dose, cell line and timepoint as having significant impact on the output. We discuss the biological relevance of these four factors and incorporate them into a work flow.
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http://dx.doi.org/10.1016/j.tox.2019.05.008DOI Listing
July 2019

Obstetric outcomes and effects on babies born to women treated for epilepsy during pregnancy in a resource limited setting: a comparative cohort study.

BMC Pregnancy Childbirth 2018 Jun 14;18(1):230. Epub 2018 Jun 14.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.

Background: Management of epilepsy during pregnancy in a resource-limited setting (RLS) is challenging. This study aimed to assess obstetric outcomes and effects on babies of women with epilepsy (WWE) exposed to Anti-epileptic drugs (AEDs) compared to non-exposed controls in a RLS.

Methods: Pregnant WWE were recruited from antenatal and neurology clinics of a tertiary care hospitals in Sri Lanka. Patients were reviewed in each trimester and post-partum. Medication adherence, adverse effects, seizure control and carbamazepine blood levels were monitored. Post-partum, measurements for anthropometric and dysmorphic features of the babies and congenital abnormalities were recorded. Age and sex matched babies not exposed to AED recruited as controls were also examined.

Results: Ninety-six pregnant WWE were recruited (mean period of gestation 22.9 weeks). Mean age was 28 years and 48(50%) were primigravidae. Fifty percent (48) were on monotherapy, while 23.8, 15.9 and 4.1% were on two, three and four AEDs respectively. AEDs in first trimester (TM1) were carbamazepine (71%), valproate (25.8%) clobazam (29.5%), lamotrigine (7%) topiramate (5%) and others (3.4%). Sodium valproate use reduced significantly from T1 to T2(p < 0.05). Sub-therapeutic carbamazepine levels correlated positively (r = 0.547) with poor medication adherence (p = 0.009) and negatively (r = 0.306) with adverse effects (p = 0.002). Seventy-six WWE completed follow-up reporting w 75 (98.6%) live births and one T1 miscarriage (1.3%). Three (4.3%) were preterm. Majority (73.33%) were normal vaginal deliveries. Cesarean sections were not increased in WWE. Fifty-nine (61.45%) babies were examined. For those examined during infancy, 53 age and sex matched controls were recruited and examined.. Congenital abnormalities occurred in 5 (9.43%) babies of WWE [atrio-ventricular septal defect (2), renal hypoplasia (1), cryptorchidism (1), microcephaly (1)] compared to 2 (3.77%) in controls (2 microcephaly; p = 0.24). Fetal exposure to AEDs increased a risk of low birth weight (RR 2.8; p = 0.049). Anthropometric parameters of AED exposed babies were lower at birth but not statistically significant between the two groups (weight p = 0.263, length p = 0.363, occipito-frontal circumference (OFC) p = 0.307). However, weight (p = 0.009), length (p = 0.016) and OFC (p = 0.002) were significantly lower compared to controls at an average of 3.52 months.

Conclusion: Most pregnancies are unplanned in the RLS studied, and AEDs were altered during pregnancy. Congenital anomalies occurred at rates comparable to previous reports. Fetal exposure to AED had growth retardation in infancy compared to non-exposed babies.
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http://dx.doi.org/10.1186/s12884-018-1857-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000926PMC
June 2018

Grouping 34 Chemicals Based on Mode of Action Using Connectivity Mapping.

Toxicol Sci 2016 06 29;151(2):447-61. Epub 2016 Mar 29.

*Mason Business Center, The Procter & Gamble Company, Cincinnati, Ohio 45040 and.

Connectivity mapping is a method used in the pharmaceutical industry to find connections between small molecules, disease states, and genes. The concept can be applied to a predictive toxicology paradigm to find connections between chemicals, adverse events, and genes. In order to assess the applicability of the technique for predictive toxicology purposes, we performed gene array experiments on 34 different chemicals: bisphenol A, genistein, ethinyl-estradiol, tamoxifen, clofibrate, dehydorepiandrosterone, troglitazone, diethylhexyl phthalate, flutamide, trenbolone, phenobarbital, retinoic acid, thyroxine, 1α,25-dihydroxyvitamin D3, clobetasol, farnesol, chenodeoxycholic acid, progesterone, RU486, ketoconazole, valproic acid, desferrioxamine, amoxicillin, 6-aminonicotinamide, metformin, phenformin, methotrexate, vinblastine, ANIT (1-naphthyl isothiocyanate), griseofulvin, nicotine, imidacloprid, vorinostat, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) at the 6-, 24-, and 48-hour time points for 3 different concentrations in the 4 cell lines: MCF7, Ishikawa, HepaRG, and HepG2 GEO (super series accession no.: GSE69851). The 34 chemicals were grouped in to predefined mode of action (MOA)-based chemical classes based on current literature. Connectivity mapping was used to find linkages between each chemical and between chemical classes. Cell line-specific linkages were compared with each other and to test whether the method was platform and user independent, a similar analysis was performed against publicly available data. The study showed that the method can group chemicals based on MOAs and the inter-chemical class comparison alluded to connections between MOAs that were not predefined. Comparison to the publicly available data showed that the method is user and platform independent. The results provide an example of an alternate data analysis process for high-content data, beneficial for predictive toxicology, especially when grouping chemicals for read across purposes.
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http://dx.doi.org/10.1093/toxsci/kfw058DOI Listing
June 2016

A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.

Toxicology 2015 Feb 2;328:29-39. Epub 2014 Dec 2.

Mason Business Center, The Procter & Gamble Company, Cincinnati, OH 45040, USA.

High-content data have the potential to inform mechanism of action for toxicants. However, most data to support this notion have been generated in vivo. Because many cell lines and primary cells maintain a differentiated cell phenotype, it is possible that cells grown in culture may also be useful in predictive toxicology via high-content approaches such as whole-genome microarray. We evaluated global changes in gene expression in primary rat hepatocytes exposed to two concentrations of ten hepatotoxicants: acetaminophen (APAP), β-naphthoflavone (BNF), chlorpromazine (CPZ), clofibrate (CLO), bis(2-ethylhexyl)phthalate (DEHP), diisononyl phthalate (DINP), methapyrilene (MP), valproic acid (VPA), phenobarbital (PB) and WY14643 at two separate time points. These compounds were selected to cover a range of mechanisms of toxicity, with some overlap in expected mechanism to address the question of how predictive gene expression analysis is, for a given mode of action. Gene expression microarray analysis was performed on cells after 24h and 48h of exposure to each chemical using Affymetrix microarrays. Cluster analysis suggests that the primary hepatocyte model was capable of responding to these hepatotoxicants, with changes in gene expression that appear to be mode of action-specific. Among the different methods used for analysis of the data, a combination method that used pathways (MOAs) to filter total probesets provided the most robust analysis. The analysis resulted in the phthalates clustering closely together, with the two other peroxisome proliferators, CLO and WY14643, eliciting similar responses at the whole-genome and pathway levels. The Cyp inducers PB, MP, CPZ and BNF also clustered together. VPA and APAP had profiles that were unique. A similar analysis was performed on externally available (TG-GATES) in vivo data for 6 of the chemicals (APAP, CLO, CPZ, MP, MP and WY14643) and compared to the in vitro result. These results indicate that transcription profiling using an in vitro assay may offer pertinent biological data to support predictions of in vivo hepatotoxicity potential.
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http://dx.doi.org/10.1016/j.tox.2014.11.008DOI Listing
February 2015

TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin.

Toxicol Appl Pharmacol 2014 May 24;276(3):171-8. Epub 2014 Feb 24.

Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Pathology, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:

The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highly induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed that MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial-stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin.
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http://dx.doi.org/10.1016/j.taap.2014.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137792PMC
May 2014

Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Toxicol Appl Pharmacol 2011 Apr 4;252(2):150-8. Epub 2011 Feb 4.

The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA.

Exposure to the aryl hydrocarbon receptor (AHR) agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters B-cell differentiation and suppresses antibody production. Previous genomic studies in mouse B cells identified Bach2 as a direct target of the AHR. Bach2 is known to repress expression of Prdm1, a key transcription factor involved in B-cell differentiation, by binding to Maf elements (MAREs) in the regulatory regions of the gene. Chromatin immunoprecipitation followed by quantitative PCR in TCDD-treated lipopolysaccharide (LPS)-activated B cells showed increased binding of the AHR within the first intron in the Bach2 gene. The binding was further confirmed by electrophoretic mobility shift assay (EMSA). TCDD also induced expression of Bach2 in activated as well as resting B cells from 2 to 24h post-treatment in a time- and concentration-dependent manner. Expression of Prdm1 was decreased by TCDD at 24h and was consistent with repression by Bach2. Increased DNA binding activity to the intron 5 MARE with increasing TCDD concentrations was observed by EMSA. Supershifts identified the presence of Bach2 in the DNA binding complex associated with the intron 5 MARE of Prdm1. Functional validation of the role of Bach2 in the suppression of B-cell differentiation by TCDD was performed using RNA interference (RNAi). Knockdown of Bach2 showed approximately 40% reversal in the TCDD-induced suppression of IgM secretion when compared to controls. The results suggest that the transcriptional regulation of Bach2 by the AHR is one of the mechanisms involved in the suppression of B-cell differentiation by TCDD.
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http://dx.doi.org/10.1016/j.taap.2011.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106294PMC
April 2011

An integrated genomic analysis of aryl hydrocarbon receptor-mediated inhibition of B-cell differentiation.

Toxicol Sci 2010 Dec 6;118(2):454-69. Epub 2010 Sep 6.

The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA.

The aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters differentiation of B cells and suppresses antibody production. A combination of whole-genome, microarray-based chromatin immunoprecipitation (ChIP-on-chip), and time course gene expression microarray analysis was performed on the mouse B-cell line CH12.LX following exposure to lipopolysaccharide (LPS) or LPS and TCDD to identify the primary and downstream transcriptional elements of B-cell differentiation that are altered by the AHR. ChIP-on-chip analysis identified 1893 regions with a significant increase in AHR binding with TCDD treatment. Transcription factor binding site analysis on the ChIP-on-chip data showed enrichment in AHR response elements. Other transcription factors showed significant coenrichment with AHR response elements. When ChIP-on-chip regions were compared with gene expression changes at the early time points, 78 genes were identified as potential direct targets of the AHR. AHR binding and expression changes were confirmed for a subset of genes in primary mouse B cells. Network analysis examining connections between the 78 potential AHR target genes and three transcription factors known to regulate B-cell differentiation indicated multiple paths for potential regulation by the AHR. Enrichment analysis on the differentially expressed genes at each time point evaluated the downstream impact of AHR-regulated gene expression changes on B-cell-related processes. AHR-mediated impairment of B-cell differentiation occurred at multiple nodes of the B-cell differentiation network and potentially through multiple mechanisms including direct cis-acting effects on key regulators of B-cell differentiation, indirect regulation of B-cell differentiation-related pathways, and transcriptional coregulation of target genes by AHR and other transcription factors.
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http://dx.doi.org/10.1093/toxsci/kfq265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003543PMC
December 2010

Is walking barefoot a risk factor for diabetic foot disease in developing countries?

Rural Remote Health 2007 Apr-Jun;7(2):692. Epub 2007 Jun 15.

Department of Clinical Medicine, Faculty of Medicine, Colombo, Sri Lanka.

Introduction: Walking barefoot is common in poorer developing countries which have large rural populations. Although high rates of foot injury could be expected among those who walk barefoot, walking barefoot as a risk factor for diabetic foot disease is rarely documented in the literature.

Methods: Two preliminary clinical studies were undertaken to investigate whether there is a causal link between walking barefoot and diabetic foot ulcers. The first study investigated whether being barefoot was a factor in initiating foot ulceration. In the second study, 204 consecutive diabetic outpatients were studied to further investigate the association between diabetic foot disease and walking barefoot.

Results: In the first study, of the 75 consecutive diabetics admitted for foot ulceration of less than 4 weeks, 32 (42.4%) had foot ulcers resulting from injuries by sharp or hard objects. Of those injured, 27 (84%) were barefoot at the time of the injury. This suggested that walking barefoot is a risk factor for foot ulcers, and that using footwear has the potential to prevent foot ulcers. In the second study, the relative risk of foot ulcers among barefoot diabetics was 2.21 (95% CI 1.55 to 3.14) compared with those using some form of footwear. A history of foot ulcers was more frequent in the group who wore footwear less than 10 hours per day, compared with those who used footwear more than 10 hours. The prevalence of web space and nail infections was also higher in the group who wore footwear less than 10 hours per day, compared with those who used footwear for more than 10 hours.

Conclusion: The data suggest that walking barefoot is a risk factor for diabetic foot disease. Thus, public health messages in developing countries with large rural populations who walk barefoot should strongly advise diabetics to use footwear for a greater part of the day. This may be overlook in literature originating from affluent countries where footwear use is the norm. Further studies are indicated to investigate potential associations between walking barefoot, rurality and cultural factors.
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August 2007

Sugars, fruits and fructose drinks.

Ceylon Med J 2004 Mar;49(1):24

Department of Pharmacology, Faculty of Medicine, Colombo.

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http://dx.doi.org/10.4038/cmj.v49i1.3281DOI Listing
March 2004

Fish bone migration.

Ceylon Med J 2001 Sep;46(3):99

Department of Pharmacology, Faculty of Medicine, Colombo.

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http://dx.doi.org/10.4038/cmj.v46i3.8134DOI Listing
September 2001

All that glitters in glitazones.

Ceylon Med J 1999 Dec;44(4):184-5

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December 1999

Patient mixed biphasic insulin in a diabetic clinic.

Ceylon Med J 1997 Sep;42(3):137-8

Department of Clinical Medicine, Faculty of Medicine, University of Colombo.

Introduction: Improved glycaemic control is possible with the use of multiple injections of premixed insulin. These are expensive, and not available in state hospitals.

Objectives: To study the cost, patient acceptance and efficacy of a patient mixed and administered combination of soluble and lente (biphasic) insulin administered twice a day.

Patients: A cohort of 25 patients with poor glycaemic control on a single dose of 100 units or more of lente insulin. 25 patients matched for age and glycaemic control were used as a control.

Setting: The diabetic clinic of the National Hospital Sri Lanka.

Method: A prospective study of a cohort of patients.

Results: Mean fasting blood glucose decreased from 8.3 mmol/l (SD 3.1) to 6.9 mmol/l (SD 2.3, p < 0.01) and mean blood glucose levels declined from 12.3 mmol/l (SD 4.1) to 10.1 mmol/l (SD 4.7, p < 0.01) in the biphasic group. Total mean insulin dose fell from 80 units (SD 12) to 61 units (SD 11) in the biphasic group, but increased in the control group from 82 units (SD 16) to 91 units (SD 13.1). The diabetes well-being score in the biphasic group was 91.5 (SD 35.3), while the control group had a score of 63.7 (SD 21.3 p < 0.01). Mean glycosylated haemoglobin (HbA1c %) was 8.1 (SD 2.7) in the biphasic group compared to 9.2 (SD 3.3) in the control group.

Conclusion: Patient mixed and administered biphasic insulin on a twice daily basis is feasible, acceptable to patients, results in better glycaemic control and affords better patient satisfaction.
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September 1997

An audit of structure, process and outcome of care of the diabetic clinic, National Hospital of Sri Lanka.

Ceylon Med J 1997 Sep;42(3):133-6

Department of Medicine, Faculty of Medicine, Colombo.

Aims: To audit the structure, process and outcome of care.

Setting: The diabetic clinic, National of Hospital Sri Lanka (NHSL).

Methods: A previously validated MCQ paper of 10 questions which assessed knowledge of diabetes on insulin therapy, dietary management, management during acute illness and management of emergencies was administered to all patients. The function of the clinic was assessed using previously validated audit case record forms.

Measures Of Outcome: Diabetes knowledge among patients, waiting times, bypassing of local institutions, availability of diagnostic equipment, screening activities and time spent for consultation.

Results: The clinic had a daily average attendance of 186 patients seen between 0800 to 1200 hours. A single medical officer spent 2.1 minutes for each patient. No screening was performed. There were no facilities to examine patients or for them to sit during consultation. The diabetes knowledge score was 15.1 (SD 3) from a maximum score of 40.43% had bypassed a local institution. Reasons for bypass included non-availability of drugs and the expectation of quality care at NHSL. Patients spent a mean of 1.5 (SD 0.7) hours travelling to the clinic and waited a mean of 1.56 (SD 0.4) hours to see the doctor and 1.3, (SD 0.12) hours to obtain drugs.

Conclusions: The services of the diabetic clinic do not meet the standards expected of a clinic at a tertiary referral centre. Lack of planning and resources (space, manpower and management skills) can be identified as principal shortcomings.
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September 1997

Post-renal transplant diabetes in Sri Lanka.

Transplant Proc 1996 Jun;28(3):1945-7

Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.

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June 1996

Dermoid cyst of the caecum.

Authors:
K M Abrew M Hughes

Ceylon Med J 1993 Jun;38(2):92-3

Gwynedd District General Hospital, Bangor, U.K.

Dermoid cysts of the caecum are rare and only four cases have been reported in the literature. They are sequestration cysts and are lined by squamous epithelium with skin appendages. Aetiologically these cysts may represent squamous metaplasia of enterogenous cysts or sequestration cysts due to epidermal inclusion at the time of closure of the neural groove.
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June 1993

Living related donor kidney transplantation in Sri Lanka.

Transplant Proc 1992 Oct;24(5):1816-7

Faculty of Medicine, University of Colombo, Sri Lanka.

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October 1992

Living related donor kidney transplantation in Sri Lanka.

Transplant Proc 1992 Oct;24(5):1816-7

Faculty of Medicine, University of Colombo, Sri Lanka.

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October 1992