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Biomedical subjects

C Roberts

Publications and source records attributed to C Roberts.

At least 55 records · Page 3Linked to original sources

A clinical validation of the Dysmorphic Concern Questionnaire.

OBJECTIVE: The current study addressed the concept of dysmorphic concern as a symptom that may exist in a number of disorders. The aims of the study were to: (i) validate a recently developed questionnaire that measures dysmorphic concern, the Dysmorphic Concern Questionnaire (DCQ); and (ii) evaluate the relationship of dysmorphic concern to depressed mood, social phobia, and obsessive-compulsive symptomatology. METHOD: Sixty-five psychiatric inpatients were diagnosed using the computerized version of the Composite International Diagnostic Interview (CIDI-A). They then completed the DCQ, and questionnaires measuring body dysmorphic disorder (the Body Dysmorphic Disorder Examination, or BDDE), depression, social phobia, and obsessive-compulsive disorder (OCD). The factor structure and convergent validity of the DCQ were determined, and associations with mood and anxiety symptoms explored. RESULTS: The DCQ was found to be a reliable and valid instrument that is sensitive to dysmorphic concern. Furthermore, although dysmorphic concern was associated with body dysmorphic disorder (BDD), depression, social phobia and OCD, only the score from the BDDE predicted DCQ score in a multiple regression analysis. Finally, BDD symptomatology was best defined by the presence of negative body beliefs as measured by the DCQ. CONCLUSIONS: Negative body beliefs are the hallmark of BDD. However, the existence of dysmorphic concern does not necessarily imply a diagnosis of BDD. The DCQ is a quick and efficient means of identifying dysmorphic concern in those who present with depression, OCD, social phobia or BDD.

Adolescent↗

Diploma in Hospital Infection Control: a progress report.

The Diploma in Hospital Infection Control (DipHIC) was established by the Hospital Infection Society (HIS), the London School of Hygiene and Tropical Medicine (LSHTM) and the Public Health Laboratory Service (PHLS) in 1997 and has now completed two examinations. We outline progress since the announcement of the diploma and changes to the written examination and reflective portfolio. The reflective process is described and guidance provided to active infection control practitioners wishing to consider application for the diploma by accreditation of prior learning.

Certification↗

Generation of a high-density rat EST map.

We have developed a high-density EST map of the rat, consisting of >11,000 ESTs. These ESTs were placed on a radiation hybrid framework map of genetic markers spanning all 20 rat autosomes, plus the X chromosome. The framework maps have a total size of approximately 12,400 cR, giving an average correspondence of 240 kb/cR. The frameworks are all LOD 3 chromosomal maps consisting of 775 radiation-hybrid-mapped genetic markers and ESTs. To date, we have generated radiation-hybrid-mapping data for >14,000 novel ESTs identified by our Rat Gene Discovery and Mapping Project (http://ratEST.uiowa.edu), from which we have placed >11,000 on our framework maps. To minimize mapping errors, ESTs were mapped in duplicate and consensus RH vectors produced for use in the placement procedure. This EST map was then used to construct high-density comparative maps between rat and human and rat and mouse. These maps will be a useful resource for positional cloning of genes for rat models of human diseases and in the creation and verification of a tiling set of map order for the upcoming rat-genome sequencing.

Animals↗

Retinal thickness measurements from optical coherence tomography using a Markov boundary model.

We present a system for detecting retinal boundaries in optical coherence tomography (OCT) B-scans. OCT is a relatively new imaging modality giving cross-sectional images that are qualitatively similar to ultrasound. However, the axial resolution with OCT is much higher, on the order of 10 microm. Objective, quantitative measures of retinal thickness may be made from OCT images. Knowledge of retinal thickness is important in the evaluation and treatment of many ocular diseases. The boundary-detection system presented here uses a one-dimensional edge-detection kernel to yield edge primitives. These edge primitives are rated, selected, and organized to form a coherent boundary structure by use of a Markov model of retinal boundaries as detected by OCT. Qualitatively, the boundaries detected by the automated system generally agreed extremely well with the true retinal structure for the vast majority of OCT images. Only one of the 1450 evaluation images caused the algorithm to fail. A quantitative evaluation of the retinal boundaries was performed as well, using the clinical application of automatic retinal thickness determination. Retinal thickness measurements derived from the algorithm's results were compared with thickness measurements from manually corrected boundaries for 1450 test images. The algorithm's thickness measurements over a 1-mm region near the fovea differed from the corrected thickness measurements by less than 10 microm for 74% of the images and by less than 25 microm (10% of normal retinal thickness) for 98.4% of the images. These errors are near the machine's resolution limit and still well below clinical significance. Current, standard clinical practice involves a qualitative, visual assessment of retinal thickness. A robust, quantitatively accurate system such as ours can be expected to improve patient care.

Algorithms↗

SB-236057-A: a selective 5-HT1B receptor inverse agonist.

5-HT1B autoreceptors are involved in the control of extracellular 5-HT levels from both the terminal and cell body regions of serotonergic neurons. In this manuscript we review the pharmacological and pharmacokinetic data available for the selective and potent 5-HT1B receptor inverse agonist, SB-236057-A (1'-ethyl-5-(2'-methyl-4'-(5-methyl-1,3,4-oxadiazolyl-2-yl)biphenyl-4-carbonyl)-2,3,6,7-tetrahydrospiro (furo[2,3-f]indole-3,4'-piperidine) hydrochloride). SB 236057-A has been shown to have high affinity for human 5-HT1B receptors (pK(i) = 8.2) and displays 80 or more fold selectivity for the human 5-HT1B receptor over other 5-HT receptors and a range of additional receptors, ion channels and enzymes. In functional studies at human 5-HT1B receptors SB-236057-A displayed inverse agonism (pA(2) = 8.9) using [(35)S]GTPgammaS binding, and silent antagonism (pA(2) = 9.2) using cAMP accumulation. SB-236057-A also acted as an antagonist at the 5-HT terminal autoreceptor as measured by [3H]5-HT release from electrically stimulated guinea pig and human cortical slices. In the guinea pig, pharmacokinetic analysis demonstrated that SB-236057-A was bioavailable and according to in vivo pharmacodynamic assays it enters brain and has a long duration of action. Importantly no side effect liability was evident at relevant doses from anxiogenic, cardiovascular, sedative or migraine viewpoints. In vivo microdialysis studies demonstrated that SB-236057-A is an antagonist in the guinea pig cortex but has no effect on extracellular 5-HT levels per se. In contrast, SB-236057-A increased extracellular 5-HT levels in the guinea pig dentate gyrus. This increase in 5-HT release was comparable to that observed after 14 days of paroxetine administration. SB-236057-A has been a useful tool in confirming that, in either guinea pigs or humans, the terminal 5-HT autoreceptor is of the 5-HT1B subtype. It appears that acute 5-HT1B receptor blockade, by virtue of increased 5-HT release in the dentate gyrus, may provide a rapidly acting antidepressant.

Animals↗

Evaluation of United States-licensed human immunodeficiency virus immunoassays for detection of group M viral variants.

Six Food and Drug Administration (FDA)-licensed human immunodeficiency virus type 1 (HIV-1) and HIV-1/2 immunoassays, including five enzyme immunoassays and one rapid test, were challenged with up to 250 serum samples collected from various global sites. The serum samples were from individuals known to be infected with variants of HIV-1 including group M subtypes A, B, B', C, D, E, F, and G and group O. All immunoassays detected the vast majority of samples tested. Three samples produced low signal over cutoff values in one or more tests: a clade B sample, an untypeable sample with a low antibody titer, and a group O sample. It is concluded that HIV-1 immunoassays used in the United States are capable of detecting most HIV-1 group M variants.

AIDS Serodiagnosis↗

Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast.

Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4Delta strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4Delta mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells.

Amino Acids↗

Unilateral versus bilateral acupuncture on knee function in advanced osteoarthritis of the knee--a prospective randomised trial.

We report a prospective randomised trial of acupuncture given to 44 patients with advanced osteoarthritis (OA) of the knee awaiting total knee joint replacement. Patients were randomly allocated into two groups, group A receiving acupuncture to the most affected knee only and group B receiving acupuncture to both knees. Acupuncture was given to four local points around the knee and one distal point. The local points were Spleen 9 (Yinlinquan, SP9), Spleen 10 (Xuehai, SP10), Stomach 34 (Liangqui, ST34), and Stomach 36 (Zusanli, ST36). The distal point was Large Intestine 4 (Hegu, LI4) on the first web space of the ipsilateral hand. A blinded observer assessed knee function before starting treatment, and at the end of two and six months. Analysis of the results showed a significant reduction in symptoms in both groups, and this improvement was sustained for six months. There was no statistically significant difference between the groups. In conclusion, unilateral acupuncture is as effective as bilateral acupuncture in increasing function and reducing the pain associated with OA of the knee. This trial is not able to distinguish the specific from the non-specific effects of the treatment.

Acupuncture Therapy↗

Lymphadenopathy and lymph node infarction as a result of gold injections.

This report describes a case of lymphadenopathy and lymph node infarction as a consequence of intramuscular gold administered to a patient suffering from rheumatoid arthritis, to highlight this rare association. A 34 year old woman with a four year history of rheumatoid arthritis affecting multiple joints was started on intramuscular gold injections after little response to anti-inflammatory medication. After her sixth injection the patient developed enlarged neck and axillary lymph nodes. Biopsy showed subtotal infarction of a reactive node, confirmed by histochemical, immunohistochemical, and molecular techniques. The patient continued to suffer from rheumatoid arthritis with no evidence of malignant lymphoma after three years. This case provides strong evidence that lymphadenopathy with infarction is a rare complication of gold injections. In such a situation, it is particularly important to exclude a diagnosis of lymphoma, because this is the most common cause of spontaneous lymph node infarction. This can be achieved through awareness of the association, and by the use of ancillary histochemical, immunohistochemical, and molecular techniques on the biopsy material.

Adult↗

Patient satisfaction with out of hours primary medical care.

OBJECTIVES: To describe the relationship between patient satisfaction with out of hours care provided by deputising and practice doctors in four urban areas in England and characteristics of the service provided and patients, the care given, and health outcomes. SETTING: -Fourteen general practices in four urban areas in England. PARTICIPANTS: People who requested out of hours care. DESIGN: Analysis of data from a study of out of hours care. Patients were interviewed within 5 days of their request for out of hours care. Data on the service provided were obtained from medical records and all other data were collected at interview. Satisfaction was measured using a valid reliable instrument. RESULTS: 2152 patients were recruited to the study and 1466 were interviewed. Satisfaction data were available on 1402 patients. "Overall satisfaction" was associated with age, doctor type, lack of access to a car at the time of the request, and health outcome. The relationships between satisfaction subscales and patient characteristics (age, sex, ethnicity, and access to a car at the time of the request), service characteristics (doctor type and delay between the request and visit), whether a prescription was given, and health outcome were variable. If an expected home visit was not received, "overall satisfaction" and satisfaction with "communication and management", "doctor's attitude", and "initial contact person" were reduced. CONCLUSION: Patient satisfaction is dependent on many factors. Mismatch between patient expectation and the service received is related to decreased satisfaction. This may increase as general practitioners delegate more out of hours care to cooperatives and deputising services.

Adolescent↗

School smoking policies and smoking prevalence among adolescents: multilevel analysis of cross-sectional data from Wales.

OBJECTIVE: To examine the association between school smoking policies and smoking prevalence among pupils. DESIGN: Multilevel analysis of cross-sectional data from surveys of schools and pupils. SETTING: 55 secondary schools in Wales. SUBJECTS: 55 teachers and 1375 pupils in year 11 (aged 15-16). MAIN OUTCOME MEASURES: Self-reported smoking behaviour. RESULTS: The prevalence of daily smoking in schools with a written policy on smoking for pupils, teachers, and other adults, with no pupils or teachers allowed to smoke anywhere on the school premises, was 9.5% (95% confidence interval (CI) 6.1% to 12.9%). In schools with no policy on pupils' or teachers' smoking, 30.1% (95% CI 23.6% to 36.6%) of pupils reported daily smoking. In schools with an intermediate level of smoking policy, 21.0% (95% CI 17.8% to 24.2%) smoked every day. School smoking policy was associated with school level variation in daily smoking (p = 0.002). In multilevel analysis, after adjusting for pupils' sex, parents' and best friends' smoking status, parental expectations, and alienation from school, there was less unexplained school level variation, but school smoking policy remained significant (p = 0.041). The association of smoking policy with weekly smoking was weaker than for daily smoking, and not significant after adjustment for pupil level variables. Both daily and weekly smoking prevalence were lower in schools where pupils' smoking restrictions were always enforced. Enforcement of teacher smoking restrictions was not significantly associated with pupils' smoking. CONCLUSIONS: This study demonstrates an association between policy strength, policy enforcement, and the prevalence of smoking among pupils, after having adjusted for pupil level characteristics. These findings suggest that the wider introduction of comprehensive school smoking policies may help reduce teenage smoking.

Adolescent↗

Paraoxonase status in coronary heart disease: are activity and concentration more important than genotype?

Human serum paraoxonase (PON1) hydrolyzes oxidized lipids in low density lipoprotein (LDL) and could therefore retard the development of atherosclerosis. In keeping with this hypothesis, several case-control studies have shown a relationship between the presence of coronary heart disease (CHD) and polymorphisms at amino acid positions 55 and 192 of PON1, which we associated with a decreased capacity of PON1 to protect LDL against the accumulation of lipid peroxides, but some other studies have not. However, the PON1 polymorphisms are only 1 factor in determining the activity and concentration of the enzyme. Only 3 of the previous 18 studies directly determined PON1 activity and concentration. Therefore, we studied PON1 activity, concentration, and gene distribution in 417 subjects with angiographically proven CHD and in 282 control subjects. We found that PON1 activity and concentration were significantly lower in subjects with CHD than in control subjects (activity to paraoxon 122.8 [3.3 to 802.8] versus 214.6 [26.3 to 620.8] nmol. min(-1). mL(-1), P<0.001; concentration 71.6 [11.4 to 489.3] versus 89.1 [16.8 to 527.4] microg/mL, P<0.001). There were no differences in the PON1-55 and -192 polymorphisms or clusterin concentration between patients with CHD and control subjects. These results indicate that lower PON1 activity and concentration and, therefore, the reduced ability to prevent LDL lipid peroxidation may be more important in determining the presence of CHD than paraoxonase genetic polymorphisms.

Adult↗

Expression of the protein tyrosine phosphatase-like protein IA-2 during pancreatic islet development.

A tyrosine phosphatase-like protein, IA-2, is a major autoantigen in Type 1 diabetes but its role in islet function is unclear. Tyrosine phosphorylation mediates regulation of cellular processes such as exocytosis, cell growth, and cell differentiation. To investigate the potential involvement of IA-2 in islet differentiation and insulin secretion, we analyzed by immunohistochemistry expression of IA-2 during islet development in fetal rats and during the maturation of insulin secretory responses after birth. In the fetus, IA-2 immunoreactivity was detected in primitive islets positive for insulin and glucagon at 12 days' gestation. Subsequently, IA-2 was only weakly detectable in the fetal pancreas. In neonatal rat, a progressive increase in IA-2 immunoreactivity was observed in islets from very low levels at 1 day of age to moderate labeling at 10 days. In the adult, relatively high levels of IA-2 were detected in islets, with heterogeneous expression in individual cells within each islet. IA-2 marks a population of endocrine cells that transiently appear early in pancreatic ontogeny. Islet IA-2 expression reappears after birth concomitant with the development of mature insulin secretory responses, consistent with a role for this protein in regulated hormone secretion.

Animals↗

Inflammatory endobronchial polyposis with bronchiectasis in cystic fibrosis.

An unusual case of endobronchial polyposis associated with extensive bronchiectasis in the context of cystic fibrosis (CF) has been described. A 15-yr-old female patient with CF underwent partial pneumonectomy for extensive bronchiectasis and frequent infective pulmonary exacerbations. Cylindrical bronchiectasis with associated purulent bronchitis and bronchiolitis, together with inflammatory polyposis, was noted in the resected lung. To the best of the authors' knowledge, this is the first report of multiple endobronchial polyposis and may represent a rare complication of bronchiectasis in a patient with cystic fibrosis. On-going infection and the cellular composition of the polyps are discussed in relation to their possible aetiological relevance and relationship to upper respiratory tract polyps.

Adolescent↗

Systemic antibiotics fail to clear multidrug-resistant Klebsiella from a pediatric ICU.

STUDY OBJECTIVES: To determine the magnitude of infection rate and antimicrobial resistance in a pediatric ICU (PICU), and to evaluate the efficacy of using broad-spectrum antibiotics. DESIGN: A 3-month, prospective, observational cohort audit. SETTING: A 12-bed tertiary, referral PICU. PATIENTS OR PARTICIPANTS: All children admitted to the PICU for > 72 h. INTERVENTIONS: Surveillance cultures of throat and rectum on admission and once weekly thereafter. MEASUREMENTS AND RESULTS: Of the 150 admissions during the 3-month period, a total of 52 patients (24 girls and 28 boys) requiring mechanical ventilation for a minimum of 3 days were enrolled in the audit. The median age and interquartile range (IQR) was 17 months (IQR, 5.8 to 63); length of stay, 6.5 days (IQR, 4 to 13); ventilation days, 5 (IQR, 3 to 11); pediatric risk of mortality score, 14 (IQR, 9 to 19); and risk of mortality, 0.03 (IQR, 0.014 to 0.087). Fifteen patients (29%) developed 21 infections, mainly lower-airway infections and septicemias. Of the 52 children, 7 children carried multidrug-resistant bacteria and 3 patients progressed to develop four infections with those resistant bacteria. Of the seven carriers, six patients carried gentamicin-resistant Klebsiella. Methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and gentamicin-resistant Pseudomonas aeruginosa each were carried by one child. Six of those nine resistant isolates were present in the admission flora. Despite the potent combination of piperacillin/tazobactam and amikacin, three children acquired the multidrug-resistant Klebsiella while in the PICU and became nosocomial carriers. CONCLUSIONS: Only surveillance cultures allow the distinction between import of multidrug-resistance and resistant bacteria acquired while in PICU. In this study, two thirds of the resistant isolates were imported. The introduction of newer potent systemic antibiotic combinations failed to control the endemic reservoir of multidrug-resistant Klebsiella and suggests that such policies have little impact.

Amikacin↗

Sex, ethnicity, age and education effects on the Trail Making test in a sample of cocaine abusers.

Sex, ethnicity, age and education effects on the Trail Making test (TMT), a test often used to for screen for cognitive impairment, were examined in a sample of cocaine abusers in drug abuse treatment programs. A mixed race sample of 5116 males and 2614 females was drawn from electronic files of data from the Drug Abuse Treatment Outcome Study (DATOS). The DATOS was a naturalistic, prospective cohort study that collected data from 1991-1993 in 96 programs in 11 cities in the United States. The number of cocaine/crack abuser scores available for analysis was 4306. Data were analyzed to determine the effects of sex, ethnicity, age and education variables on the two parts of the TMT in this large treatment sample of cocaine abusers. The variables of sex age, ethnicity and education were statistically significant for both parts A and B of the TMT. In addition, R-Square values for overall models were quite weak (A = .08, B = .11) suggesting that sex, ethnicity, age and education effects on the TMT, while clearly present, account for relatively little overall variance in terms of cocaine users TMT performance. These results are consistent with earlier research using a more heterogenous drug abuse treatment sample.

Adolescent↗

Using the Trail Making test to screen for cognitive impairment in a drug abuse treatment sample.

The Trail Making test (TMT) is a brief paper and pencil neuropsychological test often used for screening for cognitive impairment. The value of the TMT is examined in a sample of 5619 males and 2902 females was drawn from electronic files of data from the Drug Abuse Treatment outcome Study (DATOS), a naturalistic, prospective cohort study that collected data from 1991-1993 in 96 programs in 11 cities in the United States. Data were analyzed to determine the effects of specific drugs of abuse on parts A and B of the TMT in this large sample of patients in drug abuse treatment programs. Most subjects, regardless of type of drug abused, on TMT parts A and B appeared to fall within normal limits relative to commonly accepted cutoff scores. These results suggest that the TMT parts A and B would have great value as screening measures for cognitive impairment in a drug abuse treatment population.

Adult↗