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Biomedical subjects

L Crawford

Publications and source records attributed to L Crawford.

At least 19 recordsLinked to original sources

A single-blinded case controlled study on effects of cardiopulmonary circulation on hearing during coronary artery bypass grafting.

OBJECTIVES: To evaluate the effect of extra-corporeal (cardiopulmonary) bypass on hearing during coronary artery bypass grafting. DESIGN: Prospective (single-blinded) controlled study. SETTING: District General Hospital. PARTICIPANTS: Fifty-two patients undergoing coronary artery bypass grafting completed this study. Comparison was made between 14 control patients undergoing off-pump coronary artery bypass grafting and 38 study patients undergoing on-pump coronary artery bypass grafting. The age range of patients was 48-81 years, with 50% between 64 and 66 years. MAIN OUTCOME MEASURES: Pure tone audiograms were performed in all patients before and after coronary artery bypass grafting. Data were analysed for any significant difference between pre- and post-operative pure tone audiograms. RESULTS: Mann-Whitney U-test demonstrated no difference between the area generated between mean pre- and post-operative audiograms (P = 0.754). No significant difference between off versus on pump was demonstrated for average differences at 250-500 Hz, 4 kHz, 4-8 kHz and 8 kHz. Wilcoxon matched-pairs signed-rank test demonstrated no difference between right and left ears for each individual frequency. Spearman's test to analyse the effect on vessel number or minutes on bypass pump revealed no significant difference at 4-8 kHz (P = 0.550 for number of vessels and P = 0.276 for minutes on pump.) CONCLUSION: In this study, it was not possible to demonstrate any statistically significant deleterious effect of extra-corporeal (cardiopulmonary) bypass on hearing during coronary artery bypass grafting.

Aged↗

An evaluation of peripheral blood eosinophil/basophil progenitors following nasal allergen challenge in patients with allergic rhinitis.

OBJECTIVE: To evaluate the effect of a single nasal allergen challenge on peripheral blood eosinophil/basophil (Eo/B) progenitor cells and induced sputum eosinophil counts in subjects with allergic rhinitis. METHODS: Sixteen adults entered a sequential nasal control and allergen challenge study, outside the pollen season. Blind assessment of peripheral blood Eo/B progenitor colony forming units (CFU), induced sputum and nasal lavage cell counts was made before and 24 h after both challenges. Subjects recorded their rhinitis symptoms and nasal peak inspiratory flow, hourly at home, following both challenges. RESULTS: When comparing the values 24 h after the control vs. the allergen challenge, there were no significant differences in Eo/B progenitor CFU (control (mean, SD): 3.6 (1.0)/10(6) cells; allergen: 4.4 (1.1)/10(6) cells) or sputum eosinophils (control (median, inter-quartile range): 1.0 (0.3-1.7)%; allergen: 0.7 (0.0-1.3)%) despite a significant increase in the percentage (median (inter-quartile range) of eosinophils in nasal lavage (control: 0.6 (0.1-0.9)%; allergen; 1.9 (0.9-8.1)% and significant worsening of nasal peak inspiratory flow and rhinitis symptoms. CONCLUSIONS: Despite a significant increase in nasal symptoms and lavage eosinophil counts, a single nasal allergen challenge was not sufficient to elicit a measurable haemopoietic response in circulation, or an increase in sputum eosinophil counts.

Adult↗

Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop ADHD. Reports implicate variants of genes important for the synthesis, uptake, transport and receptor binding of dopamine in the etiology of ADHD, including DRD4, DAT1, DRD2, and DRD5. In the present study, we genotyped a large multiplex sample of ADHD affected children and their parents for polymorphisms in genes previously reported to be associated with ADHD. Associations were tested by the transmission disequilibrium test (TDT). The sample is sufficient to detect genotype relative risks (GRRs) for putative risk alleles. The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed a significant bias in transmission of the insertion (chi(2)=7.58, P=0.006) as suggested by an analysis of a subset of these families. The seven repeat allele of the DRD4 48-bp repeat polymorphism (DRD4.7) was not significantly associated with ADHD in the large sample in contrast to our earlier findings in a smaller subset. We replicate an association of a dinucleotide repeat polymorphism near the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053). No evidence for an association was found for polymorphisms in DRD2 or DAT1 in this sample. The DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240) allele of the promoter polymorphism emerge as the two DNA variants showing a significant association in this large sample of predominantly multiplex families with ADHD, with estimated GRRs of 1.7 and 1.37, respectively.

Adolescent↗

Herbal advice.

Explore the source record for details and available documents.

Accreditation↗

Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD).

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder. Evidence from twin, adoption, and family studies provide support for a genetic contribution to the etiology of ADHD. Several candidate gene studies have identified an association between a 7-repeat variant in exon 3 of the dopamine 4 receptor gene (DRD4) and ADHD. However, in spite of the positive reports finding association of the exon 3 VNTR with ADHD, several other polymorphisms within DRD4 have been identified that conceivably could contribute to risk for ADHD. Recently, another common polymorphism of the DRD4 gene has been described involving a 120-bp repeat element upstream of the 5' transcription initiation site. In this report, we describe results of analysis of the DRD4 120-bp repeat promoter polymorphism in a sample of 371 children with ADHD and their parents, using the transmission disequilibrium test (TDT). Results showed a significant preferential transmission of the 240-bp (long) allele with ADHD. Exploratory analyses of the Inattentive phenotypic subtype of ADHD strengthened the evidence for linkage. These data add further support for the role of DRD4 variants conferring increased risk for ADHD, and imply that additional studies of DRD4 and other related genes are needed.

Adolescent↗

Cerebral dominance and schizophrenia-spectrum disorders in adults with intellectual disability.

Studies of the general population without intellectual disability have suggested an association between atypical handedness and schizophrenia-spectrum disorders (SSDs). Mixed handedness is taken as an index of diminished cerebral dominance or laterality. The present study addressed the question of whether such findings extend to the neurodevelopmentally 'at risk' population of adults with intellectual disability and SSDs compared with appropriate controls. Fourteen patients with a dual diagnosis of intellectual disability and SSD were compared with 14 controls with intellectual disability alone. Assessments of self-reported hand preference and relative hand skill were completed. Self-report of hand preference revealed highly significantly greater mixed-handedness in the SSD group. Furthermore, relative hand skill performance was significantly diminished for the dominant hand. The discrepancy between dominant and non-dominant hand functioning was lower in the SSD group and this association was highly significant. The results of the present study support the usefulness of such detailed laterality assessment in this population. Mixed laterality, over and above that of the population with general intellectual disability and developmental disorder, was associated with SSD. These results are consistent with the neurodevelopmental hypothesis of schizophrenia and its cognitive neuropsychiatric/neuropsychological sequelae.

Adult↗

External quality assessment in the examination of blood films for malarial parasites within Ontario, Canada.

OBJECTIVE: To assess laboratory practice in the examination of blood films for malarial parasites. METHOD: Ontario medical laboratories, licensed by the Ministry of Health, are required to participate in external quality assessment by the Laboratory Proficiency Testing Program, which assesses performance of laboratory assays and also examines the total testing process. Educational strategies are used to improve performance. RESULTS: A 1995 survey indicated shortcomings in detection and identification of malarial parasites in blood films. Consequently, recommendations for the investigation of malarial parasites in blood were issued. In 1996 and 1997, 16 workshops were conducted. A 1997 follow-up external quality assessment survey indicated that problems persist as 27% of laboratories failed to correctly speciate Plasmodium falciparum. Good Practice Guidelines were issued in 1998. CONCLUSION: Further education and assessment are required. Laboratories lacking expertise must establish referral arrangements with more proficient laboratories.

Animals↗

The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes.

OBJECTIVES: The purpose of this study was to assess safety and efficacy of enhanced external counterpulsation (EECP). BACKGROUND: Case series have shown that EECP can improve exercise tolerance, symptoms and myocardial perfusion in stable angina pectoris. METHODS: A multicenter, prospective, randomized, blinded, controlled trial was conducted in seven university hospitals in 139 outpatients with angina, documented coronary artery disease (CAD) and positive exercise treadmill test. Patients were given 35 h of active counterpulsation (active CP) or inactive counterpulsation (inactive CP) over a four- to seven-week period. Outcome measures were exercise duration and time to > or =1-mm ST-segment depression, average daily anginal attack count and nitroglycerin usage. RESULTS: Exercise duration increased in both groups, but the between-group difference was not significant (p > 0.3). Time to > or =1-mm ST-segment depression increased significantly from baseline in active CP compared with inactive CP (p = 0.01). More active-CP patients saw a decrease and fewer experienced an increase in angina episodes as compared with inactive-CP patients (p < 0.05). Nitroglycerin usage decreased in active CP but did not change in the inactive-CP group. The between-group difference was not significant (p > 0.7). CONCLUSIONS: Enhanced external counterpulsation reduces angina and extends time to exercise-induced ischemia in patients with symptomatic CAD. Treatment was relatively well tolerated and free of limiting side effects in most patients.

Adult↗

Calculation vs calibration curve for INR determination. Results of an interlaboratory proficiency scheme.

We surveyed 271 laboratories participating in a quality assessment program to ascertain whether the use of a calibration curve for determining the international normalized ratio (INR) would improve interlaboratory accuracy and precision. Lyophilized warfarinized samples with INR values assigned through manual calibration against internationally assigned rabbit reference thromboplasts were assayed for prothrombin time. Calibration analysis on the results was performed by linear regression. In all but 1 sample, the mean INR value computed by the calibration method was closer to the "true" value than the mean for the conventional calculation method using the International Sensitivity Index (ISI); the ISI calculation consistently overestimated the true value. Interlaboratory variation decreased using the calibration method. Variation from reagent to reagent was greater than from instrument to instrument, but was reduced by the calibration method. The specificity of the ISI for instrument type did not seem to alter the findings. Use of in-house calibrators to verify the ISI improved precision but not necessarily accuracy. The formation of a stable calibration line is consistent over time, but further studies are required to confirm whether such calibration improves the accuracy and precision of INR determination in practice.

Animals↗

Detection of virtually all mutations-SSCP (DOVAM-S): a rapid method for mutation scanning with virtually 100% sensitivity.

Dideoxy fingerprinting (ddF) was used as a tool to search for a generic set of conditions with sufficient power to detect virtually all mutations. For each condition tested, a very large sample of mutation-containing, single-stranded segments (about 1500) were analyzed with ddF. Correlation coefficients identified pairs of conditions in which single-strand conformation polymorphism (SSCP) mobilities were poorly correlated. The data strongly suggest that tertiary structure (e.g., base-sugar and sugar-sugar interactions) rather than secondary structure is the predominant determinant of mobility shifts by SSCP. Five conditions were selected with sufficient redundancy to detect all the mutations. The sensitivity of detection of virtually all mutations-SSCP (DOVAM-S) was determined by blinded analyses on samples containing additional mutations scattered throughout the eight exons and splice junctions in the factor IX gene. The factor IX gene sequence (2.5 kb) was scanned in one lane by 15 PCR-amplified segments (125 kb of sequence scanned per gel). All of the 84 single-base substitutions were detected in the blinded analyses, the first consisting of 50 hemizygous mutant and wild-type (WT) samples and the second consisting of 50 heterozygous mutant and WT samples. DOVAM-S is estimated to be five times faster than fluorescent DNA sequencing for the detection of virtually all mutations when the five conditions are applied.

Biotechnology↗

Early-onset periodontitis associated with Down's syndrome--clinical interventional study.

Individuals with Down's syndrome (DS) have an increased prevalence of periodontal disease compared with otherwise normal, age-matched control groups and other mentally handicapped patients of similar age distribution. The exaggerated immune-inflammatory response of the tissues cannot be explained by poor oral hygiene alone and might be the result of an impaired cell-mediated and humoral immunity and a deficient phagocytic system. As far as the progression and severity of destruction, the oral manifestations of DS patients are consistent with the juvenile periodontitis (JP) disease pattern. The purpose of the present study was 1) to assess the periodontal clinical and microbiological status of 10 DS patients aged 20 to 31 years (mean: 26.3 years) relative to that of 11 patients with cerebral palsy (CP) aged 23 to 53 years (mean: 36 years) without defective immunological functions, and 2) to determine the effect of supragingival plaque control and oral hygiene instruction in these patient groups. Subsequent to the initial examination and a professional tooth cleaning program, clinical and microbiological parameters were monitored over a period of 12 weeks. The clinical examination included the recording of plaque index (P1), gingival index (GI), probing depth (PD), and clinical attachment level (CAL). Subgingival plaque samples were always obtained from the same pocket with the highest disease activity (deepest bleeding site at baseline examination) in each subject for a morphotype analysis by dark field microscopy and for identification and quantitation of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Eikenella corrodens, Bacteroides forsythus, Fusobacterium nucleatum, Treponema denticola, and Campylobacter rectus by DNA probes. The results of the baseline examinations demonstrated that DS patients and patients with cerebral palsy had inflamed gingiva associated with a high amount of plaque. The mean probing depth and percentage of sites with probing depth> 4 mm corresponded to age and poor oral hygiene in CP patients. Deep pockets in DS patients demonstrated a high prevalence of periodontal disease compared with age-matched children with mental retardation and non-handicapped patients. Regarding the young age of onset, the severe destruction of periodontal tissues and pathogenesis of periodontitis in DS patients are consistent with the juvenile periodontitis disease pattern. The missing clinical benefit and alteration of the subgingival flora following supragingival plaque control in DS patients underlined the alteration in the immunological response.

Adult↗

The human papillomavirus type 16 E7 protein is associated with the nucleolus in mammalian and yeast cells.

In this study we show, by immunofluorescence and electron microscopy immuno-gold labelling, that the major transforming protein of Human Papillomavirus type 16 E7 is associated with the nucleolus of cells derived from the HPV16-positive cervical carcinoma line CaSki. The E7 nucleolar staining appeared to be cell cycle dependent, being considerably reduced in the G2 phase. The total level of the protein in the cell, however, remained constant during all phases. We also show that the cellular protein Rb1, which is targeted by E7, is localised in the nucleus and nucleolus in CaSki cells. Thus, it is possible that the presence of E7 in the nucleolus correlates with a hypothetical function(s) of Rb1 in this particular intranuclear compartment. The nucleolar localisation of HPV16 E7 protein was also observed in the fission yeast Schizosaccharomyces pombe, suggesting that a targeting mechanism of HPV16 E7 protein into the nucleolus is common to both mammalian and yeast systems. Nucleolar localisation of HPV16 E7 protein may be independent from Rb1 since no Rb1 related proteins have been identified in fission yeast.

Antibodies, Monoclonal↗

Proficiency testing of hemoglobinopathy techniques in Ontario laboratories.

The Laboratory Proficiency Testing Program has been in effect for 20 years. During the past 6 years, samples were distributed for screening, investigation, and identification of hemoglobinopathies to test laboratory proficiency. Six samples for hemoglobin (Hb) S screening were distributed to from 37 to 163 laboratories that perform screening tests for sickle cell disease, and 10 samples were distributed to from 52 to 71 laboratories that perform Hb electrophoresis. Assessment of unacceptable results was based on clinical significance of the errors; educational follow-up was implemented to address these results. Most participants demonstrated acceptable performance. The error rates for sickle cell screening were 2.7% to 19.7%; the poorest performance was noted for Hb SC disease. The error rates for Hb electrophoresis were 1.4% to 36.8%; the poorest performance was noted in the investigation of Hb H disease and alpha-thalassemia trait. Improved survey performance was observed in the screening for Hb S trait and in the investigation of Hb H disease, which illustrates the benefits of proficiency testing and its positive effect on laboratory services.

Certification↗

Comparison of infrared ear thermometer derived and equilibrated rectal temperatures in estimating pulmonary artery temperatures.

OBJECTIVES: To investigate the clinical accuracy of infrared ear thermometer derived and equilibrated rectal temperatures in estimating core body temperature. The clinical bias (i.e., mean difference between body sites), and variability (SD of the differences) of simultaneous temperatures were compared with pulmonary artery temperatures. Clinical repeatability (pooled SD of triplicate reading differences) was also examined for three ear infrared thermometers. DESIGN: Prospective clinical study. SETTING: A multidisciplinary, adult intensive care unit. PATIENTS: Twenty patients with an existing pulmonary artery catheter were studied in a multidisciplinary, adult intensive care unit. INTERVENTIONS: A single operator using optimum ear infrared technique and masked to ear and rectal temperatures recorded triplicate measurements with each of three infrared ear thermometers, each over a 4-min period with each infrared thermometer, while an assistant recorded temperatures. Infrared and rectal temperatures were compared with a simultaneous pulmonary artery temperature. MEASUREMENTS AND MAIN RESULTS: Infrared ear thermometers and rectal thermometers were calibrated daily, and pulmonary artery catheters were calibrated on removal from the patient. Patients were grouped into afebrile and febrile groups, based on initial pulmonary artery temperature. Bias and variability were compared between thermometers using analysis of variance. Clinical bias, but not variability, was significantly different between three ear infrared thermometers (0.16 +/- 0.46 degrees C, 0.07 +/- 0.38 degrees C, and -0.22 +/- 0.47 degrees C). The repeatability was not different between ear infrared thermometers (range 0.13 degrees C to 0.14 degrees C). Rectal temperature had a significantly greater bias (average 0.3 degrees C), but less variability (average 0.2 degrees C). Bias was increased, and variability decreased for both rectal and infrared ear temperatures when pulmonary artery temperature was increased. CONCLUSIONS: The three infrared ear thermometers studied provided a closer estimate of core body temperature than equilibrated rectal temperature. Clinical bias was greatest in febrile vs. afebrile intensive care unit patients.

Adult↗

Serological responses to human papillomavirus type 6 and 16 virus-like particles in patients with cervical neoplastic lesions.

Serum samples from 36 cervical carcinoma patients, 33 patients with high-grade squamous intraepithelial lesions, and 31 cytologically normal women were tested by enzyme-linked immunosorbent assay (ELISA) using human papilloma virus type 6 (HPV 6) and HPV 16 virus-like particles as antigens. Forty serum specimens from 1-year-old children were used to assign cutoff points. When serum samples from the subjects infected with HPV 16 were tested in an HPV 16 ELISA detecting immunoglobulin A (IgA), IgG, and IgM binding, 61% showed IgA, 44% showed IgG, and 39% showed IgM reactivity. Of HPV 6- or 11- or HPV 18-infected subjects. fewer than 17% showed IgA or IgG responses and 33% showed IgM reactivity. In contrast, 13% showed IgA, 10% showed IgG, and 16% showed IgM reactivity in the HPV DNA-negative controls. The results suggest that the IgA and IgG responses are HPV 16 specific and the IgM response is cross-reactive to different HPV types. On the other hand, the serological responses to HPV 6 did not differ in the patient and control groups. The percentages of patients positive for both IgA and IgG antibodies were significantly higher in the groups with high-grade squamous intraepithelial lesions (12% [4 of 33]; P = 0.04) and cancer (17% [6 of 36]; P = 0.02) than in the healty women (0% [0 of 31]), and the percentages for either IgA or IgG were higher for the cancer group (47% [17 of 36]; P = 0.01) than in the normal group (19% [6 of 31]). Most sera positive for IgA and IgG in the patient groups showed higher titers than those in the normal group. All these results suggest that high IgA and IgG responses are good indicators for estimating HPV 16 infection.

Adult↗