Biomedical subjects

M Robertson

Publications and source records attributed to M Robertson.

At least 37 records · Page 2Linked to original sources

PubMed2001

Does social deprivation in 1, 2, 3 and 4-year-old Scottish infants influence the frequency isolation of caries-associated micro-organisms?

OBJECTIVES: The aim of this study was to determine if there are associations between the level of social deprivation/affluence and the frequency isolation of caries-associated micro-organisms (Streptococcus mutans, Streptococcus sobrinus, lactobacilli and yeasts) in a large cohort of infants examined annually from 1 to 4 years of age. METHODS: DEPCAT was used to measure the socio-economic status of all consented infants (n=1099--1392) born in Dundee during a 1 year period (total n=1974). Caries-associated micro-organisms were cultured from saliva when the infants were 1, 2, 3 and 4 years of age. Standardised dental examinations were also carried out annually. Log linear analysis, which controlled for caries, was used to look for associations between DEPCAT and the isolation frequency of caries-associated micro-organisms. RESULTS: When controlling for caries, there was an association between DEPCAT and the isolation frequency of yeasts when the infants were 1 and 2 but not when 3 and 4 years old, whereas lactobacilli were associated only when the infants were 3 and 4 years old. Correlations between S. mutans and social deprivation were usually dependent on the caries status of the infants. CONCLUSIONS: The relationship between social deprivation and the isolation frequencies of caries-associated micro-organisms is complex with lactobacilli developing an association when the infants were 3 and 4 years old in contrast to yeasts which were only associated when the infants were 1 and 2 years old. Streptococcus mutans was associated with social deprivation when the infants were 2 years old and older, but dependent on caries status in the 3 and 4 year olds.

Age Factors↗

PubMed2001

Acute lower gastrointestinal bleeding as a late complication of spinal instrumentation.

Posterior or anterior fusion with spinal instrumentation is a well-known operation for scoliosis. There are multiple potential complications; the most common are blood loss during the initial surgery and wound infection. Vascular injury has been reported. However, to the authors' knowledge, acute gastrointestinal bleeding has not been reported. The authors report on a child who presented 6 years after posterior spinal instrumentation with massive acute lower gastrointestinal bleeding resulting from internal iliac artery injury and bowel perforation. The etiology, diagnosis, and management of such bleeding is reviewed.

Abscess↗

PubMed2001

The prevalence of Tourette syndrome in 13-14-year-olds in mainstream schools.

This study's aim was to estimate the prevalence and describe the clinical characteristics of Tourette syndrome (TS) in 13-14-year-old schoolchildren attending mainstream secondary schools. A three-stage ascertainment procedure was used to identify those who had TS. First, all 1012 Year 9 pupils were screened for tics using validated self-report questionnaires, which were completed by parents, teachers, and pupils. Data were available from at least one informant for 918 (90.7%) subjects. Tics were identified in 189 (18.7%) pupils. Second, families were contacted and a semistructured interview was carried out to determine whether they had TS. Finally, to ensure that the diagnosis of TS was correct, all those assessed as having TS were systematically assessed by an expert clinician in the field of TS. Seven young people were identified as fulfilling the criteria for TS, giving a minimum prevalence rate amongst 13-14-year-olds of 0.76% (95% CI 0.31 to 1.57) and a more realistic estimate of 1.85% (95% CI 1.00 to 2.95). Behavioural problems, in particular hyperkinetic disorder, were frequently associated with the TS group. These findings lend further support to the contention that the prevalence of TS in the community has hitherto been underestimated, though the symptoms may be generally milder than cases of TS presenting to clinics. This study supports the need for vigilance for TS in school-age children in primary care and in educational settings, so that children with this potentially serious disorder can be identified and assessed and effective management packages can be formulated to address their needs, when necessary.

Adolescent↗

PubMed2001

Role of JNK in hypertonic activation of Cl(-)-dependent Na(+)/H(+) exchange in Xenopus oocytes.

In the course of studying the hypertonicity-activated ion transporters in Xenopus oocytes, we found that activation of endogenous oocyte Na(+)/H(+) exchange activity (xoNHE) by hypertonic shrinkage required Cl(-), with an EC(50) for bath [Cl(-)] of approximately 3mM. This requirement for chloride was not supported by several nonhalide anions and was not shared by xoNHE activated by acid loading. Hypertonicity-activated xoNHE exhibited an unusual rank order of inhibitory potency among amiloride derivatives and was blocked by Cl(-) transport inhibitors. Chelation of intracellular Ca(2+) by injection of EGTA blocked hypertonic activation of xoNHE, although many inhibitors of Ca(2+)-related signaling pathways were without inhibitory effect. Hypertonicity activated oocyte extracellular signal-regulated kinase 1/2 (ERK1/2), but inhibitors of neither ERK1/2 nor p38 prevented hypertonic activation of xoNHE. However, hypertonicity also stimulated a Cl(-)-dependent increase in c-Jun NH(2)-terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE but not activation by acid loading. We conclude that hypertonic activation of Na(+)/H(+) exchange in Xenopus oocytes requires Cl(-) and is mediated by activation of JNK.

Amiloride↗

PubMed2001

Complete heart block and sudden death in mice overexpressing calreticulin.

The expression of calreticulin, a Ca(2+)-binding chaperone of the endoplasmic reticulum, is elevated in the embryonic heart, and because of impaired cardiac development, knockout of the Calreticulin gene is lethal during embryogenesis. The elevated expression is downregulated after birth. Here we have investigated the physiological consequences of continued high expression of calreticulin in the postnatal heart, by producing transgenic mice that overexpress the protein in the heart. These transgenic animals exhibit decreased systolic function and inward I(Ca,L), low levels of connexin43 and connexin40, sinus bradycardia, and prolonged atrioventricular (AV) node conduction followed by complete heart block and sudden death. We conclude that postnatal downregulation of calreticulin is essential in the development of the cardiac conductive system, in particular in the sinus and AV nodes, when an inward Ca(2+) current is required for activation. This work identifies a novel pathway of events, leading to complete heart block and sudden cardiac death, which involves high expression of calreticulin in the heart.

Animals↗

PubMed2001

Human cytomegalovirus a sequence and UL144 variability in strains from infected children.

Human cytomegalovirus (HCMV) displays genetic polymorphisms. This variability may contribute to strain-specific tissue tropism and disease expression in HCMV-infected humans. To determine strain variability in a sequence and UL144 gene regions, 51 low-passage isolates from 44 HCMV-infected children were studied. Isolates were obtained from 28 healthy children attending child care centers in Iowa and from 16 congenitally infected infants born in Texas. Isolates demonstrated substantial nucleotide variation in each gene region. Phylogenetic analysis of a sequence variability allowed 39 isolates to be grouped into six clades. The largest clade contained 16 isolates with > or = 95% nucleotide homology. Forty-eight of the 49 HCMV isolates yielding UL144 amplicons was grouped according to the clades described a few years ago [Lurain et al. (1999) Journal of Virology 73:10040-10050]. No linkage was observed among a sequence, UL144, and glycoprotein B (gB; UL55) polymorphisms. Four Texas and 11 Iowa isolates displayed > or = 95% sequence homology for a sequence and UL144 regions and possessed identical gB genotypes. No relationship between UL144 polymorphisms and outcome of congenital HCMV infection was observed. These data indicate that HCMV strains circulating among young children have UL144 polymorphisms similar to those of HCMV strains excreted by immunocompromised adults. Identification of conserved nucleotide sequences among Iowa and Texas children suggests genetic stability and biologic importance of these gene regions.

Base Sequence↗

PubMed2001

The Arabidopsis protein SHI represses gibberellin responses in Arabidopsis and barley.

The current model of gibberellin (GA) signal transduction is based on a derepressible system and a number of candidate negative regulators have been identified in Arabidopsis. We previously have reported the identification of the Arabidopsis gene SHORT INTERNODES (SHI) that causes suppression of GA responses when constitutively activated. In this paper, we show by using reporter gene analysis that the SHI gene is expressed in young organs, e.g. shoot apices and root tips. The model predicts a suppressor of GA responses to be active in these tissues to prevent premature growth or development. To study the effect of SHI on GA signaling, we used a functional assay that measures effects of signaling components on a well-defined GA response; the up-regulation of alpha-amylase in barley (Hordeum vulgare) aleurones in response to GA treatment. We found that SHI was able to specifically block the activity of a high-isoelectric point alpha-amylase promoter following GA(3) treatment, which further supports that SHI is a suppressor of GA responses. We have identified two putative loss-of-function insertion alleles of SHI and lines homozygous for either of the new alleles show no phenotypic deviations from wild type. Because SHI belongs to a gene family consisting of nine members, we suggest that SHI and the SHI-related genes are functionally redundant. We also show that a functional ERECTA allele is able to partly suppress the dwarfing effect of the shi gain-of-function mutation, suggesting that the erecta mutation harbored by the Landsberg erecta ecotype is an enhancer of the shi dwarf phenotype.

Alleles↗

PubMed2000

Fat redistribution in indinavir-treated patients with HIV infection: A review of postmarketing cases.

CONTEXT: Fat redistribution (FR) occurring alone or in association with hyperlipidemia has been associated with protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTIs); however, the relationship between FR features, relationship of FR to hyperlipidemia, and pathogenesis of FR is unknown. OBJECTIVE: To characterize the spectrum of FR, assess relationships among FR features, determine trends in occurrence of FR, and determine relationship of FR to hyperlipidemia. DESIGN: Review of postmarketing indinavir reports of FR in Merck & Co. Inc.'s database. SETTING AND PARTICIPANTS: 282 reports of FR among HIV-positive patients taking indinavir submitted through the passive postmarketing system to Merck through February 23, 1998. RESULTS: 282 FR reports were compared across 3 groups: fat accumulation (FA) only, FA with peripheral wasting (FA with PW), and peripheral wasting only (PWO). Of 282 reports, 56% (159 of 282) had FA only, 22% (63 of 282) had FA with PW, and 21% (60 of 282) had PWO. The proportions of reports of PWO was higher in men, whereas the proportion of reports of FA was higher in women. Blood lipids were provided in 93 of 282 reports; were elevated in 69 of 93, and were normal in 24 of 93 reports. Proportions of hyperlipidemia and hypertriglyceridemia reports were significantly higher in the PWO group versus FA only group (p =.024 and.003, respectively) and versus FA with/without PW groups (p =.038 and.005, respectively). Weight gain was more frequently reported in those with FA (100%) or FA with PW (68%), whereas weight loss was usually reported in those with PWO (83%). In all, 98% of patients reporting FR on indinavir for whom a concomitant drug history was available were also taking lamivudine, stavudine, or both. A higher proportion of patients reporting PWO (34 of 60; 56.7%) versus FA (42 of 159; 26.4%) only took both lamivudine and stavudine. CONCLUSIONS: Differences observed from analysis of cases in clinical features, gender, weight change, concomitant medications, and presence of hyperlipidemia among the three groups of FR cases reported to Merck suggests that PWO may be a distinct entity from other features of FR. The data suggest that certain antiretroviral combinations predispose HIV persons to development of FR.

Adipose Tissue↗

PubMed2000

Virological and immunological effects of combination antiretroviral therapy with zidovudine, lamivudine, and indinavir during primary human immunodeficiency virus type 1 infection.

Forty-seven patients presenting with primary human immunodeficiency virus (HIV) infection were treated with zidovudine 200 mg 3 times a day, lamivudine 150 mg 2 times a day, and indinavir 800 mg 3 times a day for 1 year. From a mean pretreatment viral RNA level of 4.93 log(10) copies/mL, the proportions of patients having <500 copies/mL at 24 and 52 weeks were 92.0% and 89.2%, respectively. For the 35 patients with data available at 24 and 52 weeks, the corresponding proportions for the <50 copies/mL analysis were 86.6% and 79.3%, respectively. The change in virus load was -2.19 and -2.41 log(10) copies/mL at weeks 8 and 52, respectively. CD4 cell counts increased, from a mean of 546 cells/mm(3), by 142 cells/mm(3) at week 24 and by 210 cells/mm(3) at week 52. Three patients discontinued the study because of drug-related toxicity. Six (12.8%) patients had adverse experiences associated with nephrolithiasis. Combination therapy with zidovudine, lamivudine, and indinavir during primary HIV infection results in a profound and sustained reduction in virus load with concurrent recovery of the CD4 cell population.

Adult↗

PubMed2000

Caries-associated micro-organisms in infants from different socio-economic backgrounds in Scotland.

OBJECTIVES: The aims of this study were: (1) to compare the frequency of isolation of mutans streptococci, (Streptococcus mutans, Steptococcus sobrinus), lactobacilli and yeasts (caries-associated micro-organisms) in the saliva of 1-year-old infants with and without dental caries; and (2) to determine if socio-economic background influenced the frequency isolation of bacteria and caries status. METHODS: 1393 1-year-old consented infants, who comprised 70. 3% of children born in Dundee during a 1year period, had saliva samples taken (tongue-loop method) for microbiological culture and were examined for dental caries (d(1)-threshold: enamel and dentine diagnostic threshold). Thirty-nine infants were diagnosed with caries and the frequencies of isolation of caries-associated micro-organisms (and absolute microbial counts) were compared with infants who were caries-free. In addition, associations were sought between the infants' socio-economic background, the frequency of isolation of caries-associated micro-organisms and caries status. RESULTS: Streptococcus mutans, lactobacilli and yeasts were isolated more frequently from those infants with caries compared to those who were caries-free (S. mutans: 29.7 vs 9.8%, P=0.0008; lactobacilli: 15.4 vs 4.3%, P=0.0073; yeasts: 23.7 vs 10.4%, P=0.0016-Fisher's exact test). There were no significant differences between the isolation frequencies of S. sobrinus (2.7 vs 1.3%, P=0.39) from those with and without caries. Significantly, more infants living in areas of high deprivation had caries compared to those from more affluent areas (DEPCAT 6 and 7 vs 1-5: 3.6 vs 1.9%, P=0.049), but, apart from yeasts, socio-economic background was not significantly associated with the isolation frequencies of any of the caries-associated micro-organisms. CONCLUSIONS: In infants as young as 1year of age, salivary S. mutans, lactobacilli and yeasts but not S. sobrinus were isolated significantly more frequently from those with caries compared to those who were caries-free. Apart from yeasts, socio-economic background did not influence the frequency of isolation of caries-associated micro-organisms. However, infants living in areas of highest deprivation had significantly higher frequencies of caries compared to those from more affluent areas.

Colony Count, Microbial↗

PubMed2000

Hypoplastic left heart syndrome: "to treat or not to treat".

OBJECTIVE: To review our experience in managing infants with hypoplastic left heart syndrome (HLHS) and to establish a consistent approach in counseling families based on our experience and on review of medical literature. METHODS: Infants were divided into three group periods based on significant changes in the approach to treatment. After a diagnosis of HLHS was made, a multidisciplinary team met the family to discuss different management options: compassionate care, active treatment by heart transplantation, or Norwood staged surgery. RESULTS: Parents of 58 infants (58%) opted for compassionate care, and 41 (42%) opted for active treatment. Seven infants underwent heart transplantation and all remain alive. A total of 27 infants underwent Norwood stage I, and 19 (70%) survived. There was a significant increase in parental choice for active treatment over the three time periods. CONCLUSION: These results indicate that HLHS can no longer be regarded as a uniformly fatal congenital anomaly. However, due to uncertainty about long-term outcome, discussion with parents should be open, and compassionate care should be presented as a management option until long-term data are available.

Euthanasia, Passive↗

PubMed2000

Choice of antibiotic and risk of colonization with vancomycin-resistant Enterococcus among patients admitted for treatment of community-acquired pneumonia.

A time-series prospective study of patients admitted to the hospital for treatment of community-acquired pneumonia was undertaken to determine vancomycin-resistant enterococcal perianal colonization rates among patients who received ceftriaxone with or without erythromycin versus those who received levofloxacin. A colonization rate of 16% (8/51) was found in the ceftriaxone-erythromycin group versus 0% (0/52) in the levofloxacin group .

Adolescent↗

PubMed2000

Relationship of Ki-ras mutations in colon cancers to tumor location, stage, and survival: a population-based study.

Some previous studies have demonstrated significant results between Ki-ras mutations and tumor stage, survival, and/or other clinical variables, whereas others have not. We therefore evaluated the significance of codons 12 and 13 Ki-ras mutations in a large population-based study of 1413 individuals with colon cancer. Ki-ras mutations were identified in approximately 32% of tumors. Codon 12 mutations were significantly more common in proximal than distal tumors (29.1% versus 20.5%; P < 0.01) and in tumors of advanced stage. Tumors from men were more likely to have transition mutations and codon 12 G-->A mutations. After adjusting for age and stage, the codon 13 G-->A mutation was associated with a 40% (95% confidence interval, 0.95-2.0) increase in short-term mortality from colon cancer. In conclusion, this population-based study demonstrates important relationships between Ki-ras mutations and stage, survival, tumor location, and gender.

Adult↗

PubMed1999

A model system for the study of human retinal angiogenesis: activation of monocytes and endothelial cells and the association with the expression of the monocarboxylate transporter type 1 (MCT-1).

AIMS/HYPOTHESIS: The growth of retinal vessels is associated with a number of disease conditions, including diabetic retinopathy and proliferative vitreo-retinopathy. In this study we describe a model of human retinal angiogenesis and show how this may be used to explain the mechanisms that are associated with the growth of new retinal vessels. METHODS: A 4 mm diameter disc of retinal tissue was placed within a fibrin matrix and the appearance was monitored daily by light microscopy. Immunohistochemical techniques were used for the detection of, glial fibrillary acidic protein, CD68, the Ki-67 antigen, vascular endothelial growth factor, monocarboxylate transporter type 1 and von Willebrand's factor. RESULTS: Vessels were evident extending from the periphery of the explant and the activation of endothelial cells was shown by immuno-peroxidase staining of paraffin embedded sections of the explants for the expression of the Ki-67 antigen, a marker of cell proliferation. The expression of glial fibrillary acidic protein and von Willebrand's factor increased with duration in culture and the presence of activated macrophages or microglia or both was shown by positive immunoreactivity for CD68 and Ki-67 and were identified by day 3. The presence of endogenous vascular endothelial growth factor and the activation of monocarboxylate transporter type 1 by vascular endothelial growth factor, showed the involvement of specific growth factors. CONCLUSION/INTERPRETATION: The explant model provides evidence for the involvement of macrophages and glial fibrillary acidic protein activation in human retinal angiogenesis and for the expression of monocarboxylate transporter type 1, which is likely to be important in the use of lactate in the hypoxic retina.

Antigens↗

PubMed1999

The identical 5' splice-site acceptor mutation in five attenuated APC families from Newfoundland demonstrates a founder effect.

Inherited mutations of the APC gene predispose carriers to multiple adenomatous polyps of the colon and rectum and to colorectal cancer. Mutations located at the extreme 5' end of the APC gene, however, are associated with a less severe disease known as attenuated adenomatous polyposis coli (AAPC). Many individuals with AAPC develop relatively few colorectal polyps but are still at high risk for colorectal cancer. We report here the identification of a 5' APC germline mutation in five separately ascertained AAPC families from Newfoundland, Canada. This disease-causing mutation is a single basepair change (G to A) in the splice-acceptor region of APC intron 3 that creates a mutant RNA without exon 4 of APC. The observation of the same APC mutation in five families from the same geographic area demonstrates a founder effect. Furthermore, the identification of this germline mutation strengthens the correlation between the 5' location of an APC disease-causing mutation and the attenuated polyposis phenotype.

Adenomatous Polyposis Coli↗

PubMed1999

Regulation of transforming growth factor-beta, basic fibroblast growth factor, and vascular endothelial cell growth factor mRNA in peripheral blood leukocytes in patients with diabetic retinopathy.

In the present study, we examined the effect of glucose concentration on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta) mRNA using reverse transcriptase-polymerase chain reaction (RT-betaCR) in normal healthy leukocytes in vitro and in leukocytes from patients with type 1 diabetes mellitus. In vitro, the level of TGF-beta mRNA was altered in response to the glucose concentration (maximum at 10 mmol/L), while bFGF mRNA remained relatively constant and VEGF mRNA varied with no clear correlation with the glucose concentration. Leukocytes from type 1 patients showed no difference in bFGF or TGF-beta mRNA levels compared with age-matched healthy controls. However, VEGF mRNA was significantly lower in type 1 patients compared with controls (P < .05). When the patients were subtyped according to the severity of retinopathy, the level of TGF-beta mRNA was elevated selectively in patients with evidence of active new retinal vessels (P < .01) and VEGF121 mRNA was reduced in patients with mild to moderate retinopathy. Thus, leukocyte growth factor mRNAs respond to acute changes in the glucose concentration in vitro, and are differentially expressed in type 1 diabetic patients during the course of the disease.

Adult↗

PubMed1999

Bonded molar tubes: a retrospective evaluation of clinical performance.

This study investigated time to first failure of stainless steel orthodontic first permanent molar tubes (Ormco Corp) bonded with a light-cured resin adhesive (Transbond) and assessed whether this was related to patient gender, age of the patient at the start of treatment, the presenting malocclusion, or the operator. All first molar tubes were bonded to intact buccal enamel, free of any restoration. Survival analysis was carried out on data from 483 patients with 1190 bonded first molar tubes. For each case, a single molar tube, either that which was first to fail or had the shortest follow-up time, was chosen for analysis. The median time until first bonded tube failure was 699 days with an overall failure rate of 21% recorded. There was no significant difference in time to first failure of molar tubes with respect to patient gender or presenting malocclusion but significant differences were recorded with respect to the patients' age at the start of treatment and the operator. Age at the start of treatment and operator were identified as independently useful predictors of bonded molar tube survival.

Adolescent↗

PubMed1999

EYA4, a novel vertebrate gene related to Drosophila eyes absent.

We have isolated a family of four vertebrate genes homologous to eyes absent (eya), a key regulator of ocular development in Drosophila. Here we present the detailed characterization of the EYA4 gene in human and mouse. EYA4 encodes a 640 amino acid protein containing a highly conserved C-terminal domain of 271 amino acids which in Drosophila eya is known to mediate developmentally important protein-protein interactions. Human EYA4 maps to 6q23 and mouse Eya4 maps to the predicted homology region near the centromere of chromosome 10. In the developing mouse embryo, Eya4 is expressed primarily in the craniofacial mesenchyme, the dermamyotome and the limb. On the basis of map position and expression pattern, EYA4 is a candidate for oculo-dento-digital (ODD) syndrome, but no EYA4 mutations were found in a panel of ODD patients.

Alternative Splicing↗