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PubMed2001

Specialist epilepsy nurses for treating epilepsy.

BACKGROUND: Epilepsy is the most common serious neurological condition after stroke, with a 0.5 per cent prevalence, and a two to three per cent life time risk of being given a diagnosis of epilepsy in the developed world. As a result of the perceived deficiencies and suggestions to improve the quality of care offered to people with epilepsy, two models of service provision have been suggested by researchers: specialist epilepsy out-patient clinics (as opposed to the management of patients in general neurology clinics or general medical clinics) and nurse-based liaison services between primary (GP) and secondary/tertiary (hospital based) care. OBJECTIVES: The aim of this review is to overview the evidence from controlled trials investigating the effectiveness of specialist epilepsy nurses compared to routine care. SEARCH STRATEGY: The following databases were searched: The Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 1999), MEDLINE, GEARS, BIDS (EMBASE=Excepta Medica), ECRI, Effectiveness Healthcare Bulletin, Effectiveness Matters, Bandolier, Evidence Based Purchasing, National Research Register, Vignettes and expert panels from Standing Group on Health Technology Assessment, PsycLit database, World Wide Web sites and reference lists of articles. SELECTION CRITERIA: All randomized controlled and quasi-randomized trials which considered specialist epilepsy nurse interventions with standard or alternative care were included in this review. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) seizure frequency (b) appropriateness of medication prescribed (c) social or psychological functioning scores (d) knowledge about epilepsy scores (e) objective measures of general health status/quality of life (f) patients' reports of information received (g) number of days spent on sick leave/missing school and employment status (h) costs of care (i) adverse effects. MAIN RESULTS: Three trials were included, two based in general practice and one in a neurology centre. The population of patients differed between trials, for example one study excluded patients with learning disabilities, and one only recruited patients with a new diagnosis. In view of this heterogeneity we decided not to pool results in a meta-analysis. As yet, there is no convincing evidence that specialist epilepsy nurses improve outcomes for people with epilepsy overall. Important outcomes (e.g. seizure frequency, psychosocial functioning, knowledge of epilepsy, general health status, work days lost, depression and anxiety scores) show no significant improvement. There is some evidence that those patients who have not had an epileptic seizure in the last six months are less at risk for depression. There is also evidence that newly diagnosed patients whose knowledge about epilepsy is poor may improve their epilepsy knowledge scores after nurse intervention. REVIEWER'S CONCLUSIONS: It is clearly plausible that specialist epilepsy nurses could improve quality in epilepsy care. However, there is as yet little evidence to support this assumption as the present research base is small. Further research is needed to investigate the effectiveness of specialist epilepsy nurses before such recommendations can be made.

Epilepsy↗

PubMed1989

Absence of toxic effects in silver reclamation workers.

Recent reports have alleged that silver presents a toxic hazard to exposed workers. To define the potential risks of long-term exposure to silver better, a cross-sectional investigation was conducted of 27 Caucasian males occupationally exposed to primarily insoluble silver compounds and 27 matched referents. Physical examination and electron microscopy of skin biopsies revealed no cases of generalized argyria. Measurements of facial discoloration, judged from color photographs by panels of laymen and physicians, showed no significant difference between the two groups. Although 29% of the silver workers and none of the referents exhibited ocular silver deposition, optometric and contrast sensitivity test results revealed no significant deficits in visual performance. The kidney and respiratory findings were essentially normal in both populations. Despite the increased presence of silver in the blood, feces, and hair of the recovery workers versus the referents, there was no evidence that chronic silver exposure adversely affected the health of these employees.

Air Pollutants, Occupational↗

PubMed2018

Quantitation of DNA Methylation by Quantitative Multiplex Methylation-Specific PCR (QM-MSP) Assay.

The defining feature of the Quantitative Multiplex Methylation-Specific PCR (QM-MSP) method to sensitively quantify DNA methylation is the two-step PCR approach for a multiplexed analysis of a panel of up to 12 genes in clinical samples with minimal quantities of DNA. In the first step, for up to 12 genes tested, one pair of gene-specific primers (forward and reverse) amplifies the methylated and unmethylated copies of the same gene simultaneously and in multiplex, in one PCR reaction. This methylation-independent amplification step produces amplicons of up to 109 copies per μL after 36 cycles of PCR. In the second step, the amplicons of the first reaction (STEP 1) are quantified with a standard curve using real-time PCR and two independent fluorophores to detect methylated/unmethylated DNA of each gene in the same well (e.g., 6FAM and VIC). One methylated copy is detectable in 100,000 reference gene copies. Methylation is reported on a continuous scale. For the gene panel, the highest level of normal DNA methylation above which a sample would be called positive is derived by using Receiver Operating Characteristic (ROC), maximizing assay specificity and sensitivity to distinguish between normal/benign versus tumor DNA. QM-MSP can be applied to clinical samples of fresh or fixed ductal cells, ductal fluid, nipple fluid, fine needle aspirates, core biopsies, and tumor tissue sections.

Breast Neoplasms↗

PubMed1998

Reversible color vision loss in occupational exposure to metallic mercury.

Color vision was evaluated in twenty-one mercury exposed workers and referents matched for sex, age, tobacco smoking, and alcohol habits. The Lanthony 15 Hue desaturated panel (D-15 d) was applied. In the workers, mean urinary Hg (HgU) was 115+/-61.5 microg/g creatinine; in all but one the values exceeded the biological limit (BEI) proposed by the American Conference of Governmental Industrial Hygienists. A dose-related subclinical color vision impairment was observed in Hg-exposed workers compared to the referents. Just after the survey, working conditions were improved. Twelve months later the workers were reexamined. Mean HgU was 10.0 microg/g creatinine and in no subjects was the BEI exceeded. Color perception was significantly improved compared to the first examination and, furthermore, no differences were observed between exposed workers and referents. The results add evidence that the color vision loss observed during the first part of the study was related to Hg exposure and, moreover, show that this effect is reversible. These data indicate that metallic Hg can induce a reversible impairment in color perception. This suggests that color vision testing should be included in studies on the early effects of Hg. The possibility of applying the D-15 d as an early effect index in the biological monitoring of Hg exposed workers should also be entertained.

Adult↗

PubMed1997

Isolation of chromosome 18-specific brain transcripts as positional candidates for bipolar disorder.

Several studies have proposed the existence of susceptibility loci for bipolar disorder on chromosome 18. To identify possible candidate genes for this disease, we isolated brain-expressed transcripts by direct cDNA selection on chromosome 18-specific biotinylated cosmid clones. Longer cognate cDNA clones of the selected cDNAs were isolated from a normalized infant brain cDNA library. Physical mapping by PCR on a panel of somatic cell hybrids was conducted by the use of primers derived from partial sequences on either the 5' or 3' ends of the clones. In our initial analysis, 48 cDNA clones were found to be chromosome 18-specific, mapping to different subchromosomal regions. Sequence redundancy among these clones yielded 30 unique transcripts, five of which were represented in previously known genes. Further sequencing of the remaining 25 unique cDNA clones confirmed the absence of significant homology to known genes, indicating that these transcripts represented novel genes. Mapping with the use of a radiation hybrid panel positioned the brain cDNAs to within = 100 to 1100 kb from reference sequence tag sites (STSs) and assembled them into six high resolution linkage groups. The majority of the transcripts were found to cluster to discrete locations on 18p and 18q, previously hypothesized as susceptibility regions for bipolar disorder, identifying them as positional candidate genes.

Bipolar Disorder↗

PubMed1993

The positions of 12 simple sequence repeat markers relative to reference loci on mouse chromosome 16.

The genetic map positions of 12 simple sequence repeat (SSR) markers spanning mouse Chromosome (Chr) 16 were determined relative to reference markers on that chromosome. Interval mapping data were obtained with a panel of DNAs from two intersubspecific backcrosses. All but one of the markers were typed by us of nonradioactive polymerase chain reaction (PCR) products analyzed on agarose gels. The marker order was determined to be Prm-1, D16Mit9, Igl-1, D16Mit29, D16Mit1/D16Mit2, Smst, D16Mit4, D16Mit11, Gap43, D16Mit14, D16Mit30, D16Mit5, Pit-1, D16Mit27, D16H21S16 (formerly D21S16h), D16Mit19, App, D16Mit7, Sod-1. Two of these markers mapped to the known human Chr 21 (HSA21)/Chr 16 conserved linkage group. Nine additional SSR markers could not be typed because they were not polymorphic (four markers), did not amplify MOLD/Rk DNA (three markers), or failed to give PCR products under a range of conditions (two markers). A subset of the most robust SSRs provide a useful marker set for the analysis of previously unmapped crosses.

Animals↗

PubMedDate not supplied

Metabolic syndrome and its association with ischemic cerebrovascular disease.

Metabolic syndrome (MS) is the term that encompasses metabolic risk factors that may lead to atherosclerotic cardiovascular disease. This study was undertaken to investigate the prevalence of MS in patients with ischemic cerebrovascular disease (CVD), according to National Cholesterol Education Program/Adult Treatment Panel III (ATP III) criteria. A total of 40 patients who were referred to the emergency department and given a diagnosis of CVD were included in this study. Detailed medical histories, physical examination findings, heights, weights, and waist circumferences of patients were recorded. Fasting blood glucose levels and lipid profiles of patients were evaluated. Those with hypertension, diabetes, or hyperlipidemia were regarded as meeting at least 1 of the ATP III criteria. Study results were compared, especially between females and males. In all, 55% of patients were female, and 70% were older than 65 y. Blood pressure over 130/85 mm Hg was assessed in 60% of patients. Among female patients, 81.8% had a waist circumference greater than 88 cm; 50% of male patients had a waist circumference over 102 cm. A fasting blood glucose level above 110 mg/dL was identified in 57.5% of patients. Serum triglyceride levels in 30% of patients were above 150 mg/L. It was noted that 33.3% of male patients had a high-density lipoprotein (HDL) level below 40 mg/L, and in 68.2% of female patients, an HDL level below 50 mg/dL was recorded. According to these findings, 14 of 22 female patients (64%) and 13 of 18 male patients (72%) were identified as having MS. High rates of stroke associated with MS reveal the importance of forthcoming preventive approaches.

Adult↗

PubMed2005

Performance of a semi-quantitative whole blood test for human heart-type fatty acid-binding protein (H-FABP).

OBJECTIVES: We evaluated the accuracy of visually reading the whole blood Rapicheck H-FABP panel test using the quantitative plasma H-FABP concentration as the reference. SUBJECTS AND METHODS: Consecutive patients with chest pain (n = 237) who were suspected of having acute myocardial infarction were recruited. The appearance of an evident test line within 5 min was given a grade of +3 (strongly positive), appearance within 15 min +2 (moderately positive) and the appearance of a weak test line within 15 min +1 (weakly positive). RESULTS AND DISCUSSION: The concordance rates were 91.8% for positive, 70.1% for negative and 80.2% for overall. Plasma H-FABP concentrations were above the cut-off value for 9.2% of negative (0) results. Fifty percent of weakly positive (+1) and 25.0% of moderately positive (+2) results had H-FABP concentrations lower than the cut-off value. All of the strongly positive (+3) were above the cut-off value. These results suggested that the false-positive and false-negative results of Rapicheck H-FABP were caused by over or underestimation in visual reading when the plasma H-FABP concentration was near the cut-off concentration. CONCLUSIONS: Low accuracy of visual reading of Rapicheck H-FABP was due to poor estimation by manual reading around the cut-off value.

Aged↗

PubMed2003

Appropriateness of choice and interpretation of tests for thrombophilic defects: a practical experience.

BACKGROUND: The use of laboratory coagulation tests in some fields of primary medicine is not well defined in available guidelines. In Italy, general practitioners tend to lack a thorough understanding of the utility of knowledge of coagulation inhibitors. METHODS: We reviewed the clinical conditions for which outpatients have been referred to our laboratory for antithrombin testing or for inherited thrombophilia tests panels over a 3-week period. Evidence-based guidelines were used to identify the appropriate requests. RESULTS: Numerous unnecessary tests were requested for both antithrombin and thrombophilia, particularly in obstetric and gynaecological situations in the setting of hormonal contraceptive treatment. CONCLUSIONS: Laboratory specialists must improve upon their communication with physicians in order to achieve an appropriate use of coagulation tests.

Blood Coagulation Tests↗

PubMed2006

Improvement of odor intensity measurement using dynamic olfactometry.

Odor intensity reveals a dose-effect relationship between inhaled odor and perceived odor sensation by the receptors, while odor concentration reflects the odor strength at the emission sources. The study reports significant improvements in experimental procedures in establishing the odor concentration-intensity (OCI) relationships using a newly developed digital olfactometer. The improvements in experimental procedures have been made to meet the requirements of both the VDI guideline 3882.1 and the European standard (EN13725). Several areas which could affect the reliability of the results have been identified in some similar studies. The latest digital olfactometer was calibrated automatically to ensure accurate and repeatable dilution ratios. Cross contamination has been eliminated through the instrument design and extensive cleaning procedures, making random presentation possible. Stringent panelist screening and continuous performance monitoring ensures consistent sensitivity of the panel. The extension of odor intensity category to temperature sensation gives a reference to assist judgments of perceived odor sensation. The DynaScent calculation method has simplified odor intensity calculation and can be applied to many odor samples. A total of 38 odor samples from three alumina refinery sites and two sewage treatment plants were collected for analysis. The results have confirmed the efficiency of the olfactometer. Distinct Odor Concentrations (DOCs) were calculated for each sample using both VDI and DynaScent methods. A student t test on two major odor types confirmed that there are no significant differences between two methods. The study has shown the DOCs for refinery odor and wastewater odor are in the range of 3.8-15.4 and 4.2-15.6 odor unit (OU)/m3 respectively. The study demonstrated that the improvements are critical in achieving reliable odor intensity measurement. This can lead to the setup of quantitative odor impact criteria for different industries and sites.

Air Pollutants↗

PubMed1999

Overuse and underuse of diagnostic upper gastrointestinal endoscopy in various clinical settings.

OBJECTIVES: To describe and compare both overuse and underuse of diagnostic upper gastrointestinal endoscopy in different settings. DESIGN: Merging of data from three prospective observational studies. The appropriateness and necessity of indications for gastroscopy were evaluated using explicit criteria developed by a standardized expert panel method (RAND-UCLA). Inappropriate endoscopies represent overuse. Necessary indications not referred for the procedure constitute underuse. SETTING: Three primary care outpatient clinics, 20 general practices, three gastroenterology practices, two district and one university hospitals. SUBJECTS: A third of the collective were consecutive ambulatory patients with upper abdominal complaints, whereas the other two thirds were ambulatory and hospitalized patients referred for the procedure. MAIN OUTCOME MEASURES: Proportions of overuse and underuse in the different settings. RESULTS: A total of 2885 patients were included (mean age, 49 years, 52% male, 2442 outpatients), 1858 patients underwent > or = 1 endoscopy. Among 2086 endoscopies, 805 (39%) were inappropriate, most of which were performed for dyspepsia (83%). Overuse was higher in young, foreign, female patients and lower in inpatient settings, the latter reflecting a different distribution of presenting symptoms. Among 1646 patient visits in primary care, overuse represented 148 endoscopies (9%). Underuse was identified in 104 of the same patient visits (6%) and was higher as patient age increased; there were no significant differences between men and women. CONCLUSIONS: Rates of overuse and underuse depend mainly on case presentation and patient characteristics. Both over- and underuse should be addressed to maintain and improve quality of care.

Adolescent↗

PubMed2001

Diversity arrays: a solid state technology for sequence information independent genotyping.

Here we present the successful application of the microarray technology platform to the analysis of DNA polymorphisms. Using the rice genome as a model, we demonstrate the potential of a high-throughput genome analysis method called Diversity Array Technology, DArT'. In the format presented here the technology is assaying for the presence (or amount) of a specific DNA fragment in a representation derived from the total genomic DNA of an organism or a population of organisms. Two different approaches are presented: the first involves contrasting two representations on a single array while the second involves contrasting a representation with a reference DNA fragment common to all elements of the array. The Diversity Panels created using this method allow genetic fingerprinting of any organism or group of organisms belonging to the gene pool from which the panel was developed. Diversity Arrays enable rapid and economical application of a highly parallel, solid-state genotyping technology to any genome or complex genomic mixtures.

Blotting, Southern↗

PubMed2004

Multiplex PCR/liquid chromatography assay for detection of gene rearrangements: application to RB1 gene.

Screening for large gene rearrangements is established as an important part of molecular medicine but is also challenging. A variety of robust methods can detect whole-gene deletions, but will fail to detect more subtle rearrangements that may involve a single exon. In this paper, we describe a new, versatile and robust method to assess exon copy number, called multiplex PCR/liquid chromatography assay (MP/LC). Multiple exons are amplified using unlabeled primers, then separated by ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC), and quantitated by fluorescent detection using a post-column intercalation dye. The relative peak intensities for each target directly reflect exon copy number. This novel technique was used to screen a panel of 121 unrelated retinoblastoma patients who were tested previously using a reference strategy. MP/LC correctly scored all deletions and demonstrated a previously undetected RB1 duplication, the first to be described. MP/LC appears to be an easy, versatile, and cost-effective method, which is particularly relevant to denaturing HPLC (DHPLC) users since it broadens the spectrum of available applications on a DHPLC system.

Base Sequence↗

PubMed2005

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Administration, Inhalation↗

PubMed2006

Prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to protective antigen that mimics vaccine-induced immunity.

The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin neutralization. This MAb was effective in prophylactic and postsymptomatic treatment of rabbits exposed to aerosolized anthrax spores, and a single intramuscular injection of 1 mg/kg of body weight fully protected cynomolgus monkeys challenged with aerosolized anthrax spores. Importantly, MAb 1303 defines a novel neutralizing epitope that requires Fc receptor engagement for maximal activity. F(ab')2 fragments of MAb 1303, which retain equivalent affinity for PA, are 10- to 100-fold less potent in neutralizing anthrax toxin in vitro. Addition of Fc receptor-blocking antibodies also greatly reduced the activity of MAb 1303. Moreover, we found that the neutralizing activity of mouse, rabbit, and human antisera elicited by PA vaccines was effectively abrogated by blocking Fc receptors. Selection of an anti-PA MAb by using a functional assay that is a surrogate for protection has resulted in the identification of a fully human MAb with potent activity in vivo and uncovered a previously unrecognized mechanism of antibody-mediated toxin neutralization that is important for currently used anthrax vaccines.

Animals↗

PubMed2004

Use of genome level-informed PCR as a new investigational approach for analysis of outbreak-associated Mycobacterium tuberculosis isolates.

Mycobacterium tuberculosis strain CH, the index isolate linked to a major tuberculosis outbreak associated with high levels of transmissibility and virulence, was characterized by microarray analysis by use of a PCR product array representative of the genome of M. tuberculosis strain H37Rv. Seven potential genomic deletions were identified in CH, five of which were confirmed by PCR analysis across the predicted deletion points. The panel of five PCRs required to individually interrogate these loci was collectively referred to as the genome level-informed PCR (GLIP) assay. GLIP analysis was performed with CH, 12 other epidemiologically linked isolates, and 43 recent, non-outbreak-associated isolates derived from patients within the local area. All 13 outbreak-linked isolates showed a profile corresponding to the presence of all five deletions. These 13 isolates were also found to share common variable-number tandem repeat and mycobacterial interspersed repetitive unit profiles. None of the 43 non-outbreak-associated isolates exhibited the five-deletion profile. Although three individual deletions were present in upwards of 44% of the non-outbreak-associated isolates, no single-deletion isolates were detected. Interestingly, none of these deletions had been previously recognized, and sequence analysis of the immediate flanking regions in CH failed to identify a likely mechanism of deletion for four of the five loci. The GLIP assay also proved valuable in ongoing surveillance of the outbreak, rapidly identifying a further two outbreak-associated cases months after the initial cluster and, importantly, dismissing a further 12 epidemiologically suspect cases, which allowed the optimum deployment of public health resources.

Base Sequence↗

PubMed1986

Inhalation of china stone and china clay dusts: relationship between the mineralogy of dust retained in the lungs and pathological changes.

A combined clinical, radiological, pathological, and mineralogical study was undertaken on 62 cases referred to the Medical Research Council Pneumoconiosis Unit by the Cardiff Pneumoconiosis Panel as Cornish china clay workers. Considerable pathological lesions were found in the lungs, both nodular and interstitial fibroses being present. Some men had worked with china stone but others had worked entirely with china clay. Nodular fibrosis appeared to be related to a high quartz content of the dust recovered from the lung, whereas among those with a high content of kaolinite dust in the lungs interstitial fibrosis was observed.

Adult↗

PubMed1998

Physician noncompliance with the 1993 National Cholesterol Education Program (NCEP-ATPII) guidelines.

BACKGROUND: We sought to determine the frequency with which physicians follow National Cholesterol Education Program (NCEP-ATPII) guidelines in screening for cardiovascular risk factors and treating hyperlipidemia. METHODS AND RESULTS: We conducted a retrospective chart review on randomly sampled charts of 225 patients admitted to the coronary care unit between January and June 1996. The main outcome measures were rates of physician screening for coronary heart disease risk factors; rates of counseling for cigarette cessation, diet, and exercise; and extent of use of NCEP algorithms for obtaining LDL cholesterol values and treating hypercholesterolemia. Screening rates for interns (who performed best) were: cigarette use (89%), known coronary heart disease (74%), hypertension (68%), hyperlipidemia (59%), family history (56%), diabetes (37%), postmenopausal hormone therapy (11%), and premature menopause (1%). Four percent of smokers were counseled to quit, 14% of patients were referred to dietitians, and 1% were encouraged to exercise. A full lipid panel was obtained in 50% of patients in whom it was indicated on the basis of NCEP criteria. Patients were more likely to receive lipid-lowering treatment if NCEP criteria indicated that they should, but 36% of hospitalized patients and 46% of patients who should have been treated on discharge were not. CONCLUSIONS: Physicians are poorly compliant with NCEP guidelines for risk factor assessment and counseling, even in patients at high risk for coronary heart disease. Physicians follow NCEP-ATPII algorithms for obtaining an LDL value, a key step in evaluating the need for treatment, only 50% of the time. NCEP criteria seem to influence the decision to initiate lipid-lowering therapy, but significant numbers of eligible patients remain untreated.

Aged↗