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PubMed1995

Quantification of a dual angiotensin I-converting enzyme-neutral endopeptidase inhibitor and the active thiol metabolite in dog plasma by high-performance liquid chromatography with ultraviolet absorbance detection.

MDL 100,240 ([4S-[4 alpha,7 alpha(R*), 12b beta]]-7-[[2- (acetylthio)-1-oxo-3-phenylpropyl]amino]-1,2,3,4,6,7,8,12b-octahyd ro-6-oxo- pyrido[2,1-a][2]benzazepine-4-carboxylic acid, I) is the thioacetyl prodrug of the active thiol, MDL 100,173 (II), a dual inhibitor of angiotensin-I converting enzyme (ACE) and neutral endopeptidase (NEP). A drug which simultaneously inhibits both ACE and NEP may provide a unique therapy for hypertension and congestive heart failure. Methods based on high-performance liquid chromatography with UV absorbance detection at 200 nm were developed to support preclinical pharmacokinetic investigations. One method is used to measure unchanged I and free II, while the second method is used to quantify the total level of the thiol II after the plasma is incubated with the disulfide reducing agent, dithiothreitol. By either method, the analytes are quantified over the range of 25-1000 ng/ml with good accuracy and precision. The overall extraction efficiencies of unchanged I and free II in dog plasma were 79% and 86%, respectively, while the extraction efficiency of total II averaged 75%. Described in this report are the results obtained in validating the assay methods for measuring the compounds in plasma. Pharmacokinetic data are presented which were obtained by applying these methods to plasma collected from dogs dosed with I.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Dual labeling of the cytoskeleton and DNA strand breaks in porcine embryos produced in vivo and in vitro.

In vitro-produced embryos exhibit decreased cell numbers, small inner cell masses and reduced pregnancy rates after transfer. Evaluation of intracellular components of in vitro-produced or -manipulated embryos will lead to improved methodology for embryo production. Whole mount techniques were developed to utilize terminal deoxynucleotidyl-transferase 3' nick end labeling (TUNEL) to detect broken DNA. Subsequent labeling of either tubulin or actin filaments provides further evidence of cytological damage. Porcine embryos produced in vitro or in vivo were evaluated throughout the cleavage and preimplantation stages of development. Early cleavage stages up to the 8-cell stage never contained TUNEL-labeled nuclei. However, TUNEL labeling of in vitro-produced morula revealed some blastomeres with broken DNA. Nearly all in vitro-produced blastocysts displayed some TUNEL positive cells, whereas in vivo-collected embryos at a similar stage displayed few, if any, TUNEL-labeled nuclei. The ratio of TUNEL-labeled DNA to total DNA area of in vitro-derived blastocysts was significantly greater than their in vivo counterparts (P < 0.05). Microtubule and microfilament labeling identified blastomeres of unequal size and shape that were losing cellular integrity. These data suggest that the combination of these labeling techniques may be useful in evaluating cellular damage in embryos produced under in vitro conditions.

Animals↗
PubMed1999

Using a dual method needs assessment to evaluate the training needs of public health professionals.

A dual method research approach was used to identify the training needs of the public health professionals in Washington. A mail questionnaire was implemented, followed by focus groups with Washington State Department of Health (DOH) and local health department (LHD) professionals. Focus groups were used successfully to enhance and clarify the survey findings by identifying the specific content of the highest rated training needs (interpersonal communication, cross-culture and cross-age communication, participatory teaching/training skills, and electronic communication) and by pinpointing preference for different modes of training delivery for different training needs.

Communication↗
PubMed2026

The effect of sex and endurance exercise training on the incretin signaling pathway in 17 rat tissues.

Incretin-based pharmacotherapies, particularly glucagon-like peptide-1 (GLP-1) receptor agonists, have transformed the treatment of type 2 diabetes, with demonstrated benefits across multiple organ systems. Their success has driven the investigation of related gut-derived hormones, most prominently dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, but extend to other targets with similar metabolic functions. For this class of drugs, the extent to which organ health improvements are secondary to improved systemic glycemic control versus direct tissue signaling remains unclear, partly because receptor availability across tissues is poorly annotated. We leveraged data from the Molecular Transducers of Physical Activity Consortium to annotate incretin receptor expression across 17 tissues in Fischer 344 rats and the Genotype-Tissue Expression Portal for human-level receptor expression. Furthermore, given the role of exercise in the preservation of muscle mass during weight loss, we analyzed the effects of 1, 2, 4, or 8 wk of treadmill exercise training on incretin-related signaling at the epigenetic, transcript, and protein levels. Endurance training elicited sex- and tissue-specific changes in incretin receptor expression, including downregulation of Gcgr across brown adipose, adrenal glands, and white adipose tissue (WAT). Training-induced Gipr regulation occurred in the adrenal glands, brain cortex, and hippocampus. Collectively, these findings contribute to the map of incretin receptor biology and identify exercise-responsive regulatory axes that may underlie synergistic effects of exercise and incretin-based therapies on weight management and metabolic health.NEW & NOTEWORTHY This study provides the first multiomic, multitissue description of incretin signaling receptor expression and regulation in response to endurance exercise training. We identify time point and sex-specific changes in incretin signaling across tissues, highlighting training effects on Gcgr, Gipr, and Sctr regulation in the adrenals, WAT, and brain. These findings help establish an exercise-responsive incretin signaling axis that may identify interactions from incretin-based therapies and exercise-based lifestyle interventions.

Animals↗
PubMed2006

Relative levels of semen platelet activating factor-receptor (PAFr) and ubiquitin in yearling bulls with high content of semen white blood cells: implications for breeding soundness evaluation.

High content of the platelet activating factor (PAF) and its plasma membrane receptor (PAFr) in semen is thought to benefit fertility in farm animals and humans. We used flow cytometric, biochemical, and immunocytochemical analysis to examine PAFr levels alone (Trial 1, n = 156 bulls) or in a dual assay with sperm defect marker ubiquitin (UBI; Trial 2, n = 88 bulls), in semen samples from 160 yearling bulls undergoing Breeding Soundness Evaluations (BSE). In both trials, we observed increased PAFr levels in semen samples with high content of white blood cells (WBC). Consequently, PAFr levels within such semen samples correlated negatively with several subjective parameters of BSE, including palpation, satisfaction of evaluation, and scrotal circumference. Due to a high WBC content, increased semen sample dilution had to be applied for microscopic evaluation. There was a negative correlation between semen PAFr and conventional sperm morphology, while the increased levels of PAFr correlated positively with sperm UBI content. Immunofluorescence microcopy revealed high expression of PAFr on the surface of leukocytes and morphologically normal spermatozoa, while reduced immunoreactivity was observed in defective spermatozoa immunoreactive to anti-UBI antibodies. A single PAFr band of appropriate mass was observed in Western blots of ejaculated spermatozoa, while testicular and epididymal spermatozoa also displayed several larger bands indicative of posttranslational processing or modification. Collectively, these data suggest that high levels of semen PAFr in young bulls are indicative of semen contamination with WBC. In the future, objective protein marker-based semen analyses in young bulls will likely require additional parameters distinguishing between marker expression in the spermatozoa and in the contaminating WBC. While identification of high sperm PAFr levels may support fertility, this assay alone is not reliable, due to the expression of PAFr in WBC that contaminate semen samples.

Animals↗
PubMed2005

G-protein alpha subunit interaction and guanine nucleotide dissociation inhibitor activity of the dual GoLoco motif protein PCP-2 (Purkinje cell protein-2).

Purkinje cell protein-2 (PCP-2; L7/GPSM4) is a GoLoco motif-containing protein that is specifically expressed in Purkinje and retinal ON bipolar cells. An alternative splice variant of PCP-2 has recently been isolated which contains two GoLoco motifs. Although the second GoLoco motif (GL2) of PCP-2 has been reported to interact with Galpha-subunits, a complete biochemical analysis of each individual motif of PCP-2 has not been performed. We demonstrate that the first GoLoco motif (GL1) of PCP-2 is equipotent as a guanine nucleotide dissociation inhibitor (GDI) towards Galphai1 and Galphai2, while it has sevenfold lower GDI activity for Galphai3 and greater than 20-fold lower GDI activity against Galphao. In contrast we found PCP-2 GL2 to be essentially equipotent as a GDI for all Galphai subunits, but it had negligible activity toward Galphao. Using co-immunoprecipitation from COS-7 cells, we found that PCP-2 was only able to interact with Galphai1 but not Galphao nor Galpha-subunits from other families (Galphas, Galphaq, or Galpha12). Mutational analysis of a non-canonical residue (glycine 24) in human PCP-2 GL1 provided evidence for heterogeneity in mechanisms of Galphai interactions with GoLoco motifs. Collectively, the data demonstrate that PCP-2 is a comparatively weak GoLoco motif protein that exhibits highest affinity interactions and GDI activity toward Galphai1, Galphai2, and Galphai3 subunits.

Amino Acid Motifs↗
PubMed2005

The Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study: methods and participant characteristics.

PURPOSE: The Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) study is one of the first population-based studies to integrate psychological, physiological, and subclinical measures of stress, disease, and mental dysfunction. This pilot study was undertaken to establish a methodology and descriptive results for a larger police study. METHODS: A stratified sample of 100 officers was randomly selected from the Buffalo, NY Police Department. Salivary cortisol served as a stress biomarker. Flow mediated dilation (FMD) and carotid intima-media thickness (IMT) were performed with ultrasound. Dual Energy X-Ray Absorptiometry (DEXA) and anthropometric measures assessed body composition. Self-report measures of depression and posttraumatic stress disorder (PTSD) were obtained. RESULTS: Recruitment attained for the study was 100%. Seventy-five percent showed a cortisol increase upon awakening, 90% a negative diurnal slope, and 77% an increased cortisol response after a high protein lunch challenge. Dexamethasone suppression was evident. FMD showed an increase in mean brachial artery diameter of 3.2% in men and 3.9% in women, and mean IMT was lower (male=0.67 mm; female=0.62 mm) compared to populations of similar age. For males, the mean body-mass index (BMI) was 29.8 kg/m2 and total body fat 23.4%. For females, the mean BMI was 26.7 kg/m2 and total body fat 31.5%. For all officers, 16% met criteria for depression; 36% reported elevated PTSD symptoms. CONCLUSIONS: Compared to populations of similar age, police officers had slightly lower FMD, lower carotid IMT, elevated BMI, and higher reported rates of depression and PTSD. Standardized physiological and psychological data collection and descriptive results confirmed that the methodology of the study is feasible in a working police population.

Adult↗
PubMed2004

Experience with family drug courts in three cities.

The purpose of the study was to describe the following components of specialized Family Drug Courts: (1) children under court supervision; (2) parent(s) named in the petition; (3) services provided and court actions taken; and (4) relapse rates. Data were collected from the court records of 65 families in three courts in Florida, Kansas, and New York. Courts differed in type of clients, sanctions used, and length of time required between drug testing. Drug testing frequency varied depending on the parent's recovery and cooperation. Test results indicated a decline in drug use in the first four months and an increased risk for relapse between the 15th and 19th weeks. Specialized Family Drug Courts show promise for an improved way to address child abuse and neglect involving parental substance use. They can also provide a unique clinical training experience for health professionals.

Adolescent↗
PubMed1997

Characterization of fetal haematopoietic progenitors circulating in maternal blood of seven aneuploid pregnancies.

A retrospective study was carried out in order to investigate the phenotype of fetal haematopoietic progenitors circulating in the maternal blood of seven aneuploid pregnancies. Five of the blood samples were taken during pregnancies affected by various fetal aneuploidies, while the other two were collected after therapeutic abortion due to prenatal cytogenetic diagnosis of trisomies 21 and 18. Haematopoietic progenitor cells, isolated by labelling the erythropoietin receptors with the biotinylated ligand before magnetic sorting and/or fibronectin cell adhesion assay, were cultured in a suitable semisolid medium. Single- or dual-colour fluorescence in situ hybridization (FISH) was utilized to identify and enumerate fetal cells amplified in culture. Fetal trisomies were confirmed in the FISH analysis with chromosome-specific probes in all the cases analysed. The fetal purity rate ranged from 16 to 26 per cent. Haematopoietic progenitors of fetal origin were found to include CFU-E, CFU-GEMM, and possibly also M-BFU-E. Interestingly, a more immature progenitor with high self-renewal capacity (CFU-blast cell) isolated by fibronectin sorting was shown to have a relatively high frequency in one case of Down syndrome. In general, the results of this study demonstrate the feasibility of diagnosing the major fetal chromosomopathies by culturing fetal cells taken from maternal blood. Furthermore, our initial data on the sequential sorting for fibronectin and erythropoietin receptors lead us to believe that this approach may broaden the range of fetal haematopoietic progenitors retrievable from the maternal circulation.

Adult↗
PubMed2006

Comparative plaque removal efficacy of a dual-action power toothbrush and a manual tooth: effects by tooth type.

PURPOSE: To evaluate the plaque removal efficacy of a dual action power toothbrush (Crest SpinBrush Pro Clean) relative to an ADA reference manual toothbrush. In addition to overall plaque removal, emphasis was put on plaque reduction around the gingival margin, interproximal areas of the tooth and in the posterior segment of the dentition. METHODS: The study was a randomized, examiner-blind, two-treatment, four-period, crossover design. After an informed consent, 50 healthy volunteers were randomized to four treatment sequences and used each toothbrush twice according to their assigned treatment sequence. At every visit, plaque removal was assessed at baseline and after a single brushing using the Rustogi-modified Navy Plaque Index that allows estimation of interproximal plaque and plaque at the gingival margin. Self-reported and examiner-observed adverse events were collected at every visit. Mean Plaque Index (MPI) scores were calculated for the whole mouth, gingival region, interproximal region and different areas of the dentition using an analysis of covariance for crossover design with baseline plaque score as the covariate. RESULTS: 49 subjects provided complete data and were included in the analysis. Baseline MPI scores were not significantly different between the groups for any investigated tooth region or dentition area. Following a single brushing, the power toothbrush provided a reduction of 43% (P< 0.001) for the whole mouth MPI, 43% (P< 0.001) for the gingival margin MPI and 65% (P< 0.001) for the interproximal MPI relative to a manual brush. Use of the power toothbrush resulted in a significant reduction of whole-mouth and gingival margin MPI across all areas of the dentition compared to a manual toothbrush (P< 0.001). The power toothbrush also had superior interproximal plaque removal efficacy compared to the manual toothbrush for molars (P< 0.001, with 118% greater removal score). Both brushes were well tolerated.

Adult↗
PubMed2003

Self-referencing intensity measurements based on square-wave gated phase-modulation fluorimetry.

An adaptation of square-wave gated phase-modulation (GPM) fluorimetry allows for self-referenced intensity measurements without the complexity of dual excitation or dual emission wavelengths. This AC technique utilizes square-wave excitation, gated detection, a reference emitter, and a sensor molecule. The theory and experimental data demonstrating the effectiveness and advantages of the adapted GPM scheme are presented. One component must have an extremely short lifetime relative to the other. Both components are affected identically by changes in intensity of the excitation source, but the sensor intensity also depends on the concentration of the analyte. The fluctuations of the excitation source and any optical transmission changes are eliminated by ratioing the sensor emission to the reference emission. As the concentration of the analyte changes, the corresponding sensor intensity changes can be quantified through several schemes including digitization of the signal and digital integration or AC methods. To measure pH, digital methods are used with Na3[Tb(dpa)3] (dpa = 2,6-pyridinedicarboxylic acid) as the long-lived reference molecule and fluorescein as the short-lived sensor molecule. Measurements from the adapted GPM scheme are directly compared to conventional ratiometric measurements. Good agreement between the data collection methods is demonstrated through the apparent pKa. For the adapted GPM measurements, conventional measurements, and a global fit the apparent pKa values agree within less than 2%. A key element of the adapted GPM method is its insensitivity to fluctuations in the source intensity. For a roughly 8-fold change in the excitation intensity, the signal ratio changes by less than 3%.

Feedback↗
PubMed1997

PET and NMR dual acquisition (PANDA): applications to isolated, perfused rat hearts.

Positron emission tomography and nuclear magnetic resonance spectroscopy are non-invasive techniques that allow serial metabolic measurements to be obtained in a single subject. Significant advantages could be obtained if both types of scans could be acquired with a single machine. A small-scale PET scanner, designed to operate in a high magnetic field, was therefore constructed and inserted into the top half of a 7.3 cm bore, 9.4 T NMR magnet and its performance characterized. The magnetic field did not significantly affect either the sensitivity (approximately 3 kcps/MBq) or the spatial resolution (2.0 mm full width at half maximum, measured using a 0.25 mm diameter line source) of the scanner. However, the presence of the PET scanner resulted in a small decrease in field homogeneity. The first, simultaneous 31P NMR spectra (200, 80 degrees pulses collected at 6 s intervals) and PET images (transverse, mid-ventricular slices at the level of the mitral value) from isolated, perfused rat hearts were acquired using a specially designed NMR probe inserted into the bottom half of the magnet. The PET images were of excellent quality, enabling the left ventricular wall and interventricular septum to be clearly seen. In conclusion, we have demonstrated the simultaneous acquisition of PET and NMR data from perfused rat hearts; we believe that the combination of these two powerful techniques has tremendous potential in both the laboratory and the clinic.

Adenosine Triphosphate↗
PubMed1998

Staff perceptions of substance use among acute psychiatry inpatients.

This paper reports on a small-scale study undertaken in two inner city acute psychiatric wards to identify the proportion of patients known to use drugs or alcohol and the perceptions of staff regarding these patients. Data collection involved a retrospective audit of patient notes and the administration of a questionnaire to nursing staff. The findings were broadly consistent with other research studies. Over half of the patient sample was reported to use illicit drugs or alcohol and in one third of cases this use was thought to have contributed to their current admission. Questionnaire results indicated that staff felt ill-equipped to offer an adequate response although all respondents welcomed opportunities to develop their knowledge and skills. The findings are discussed in light of the existing literature, and some tentative conclusions are drawn concerning the development and provision of effective integrated services for individuals with psychiatric and psychoactive substance use disorders.

Acute Disease↗
PubMed1997

Role of a C-terminal residue of an immunodominant epitope in T cell activation and repertoire diversity.

In the present study, the extent of heterogeneity in the high responder T cell response to the predominant epitope region of hen egg white lysozyme (HEL46-61) was examined. Through analyses of T cell proliferation and precursor frequency, the C3H T cell response is shown not to be limited to peptides containing the previously defined minimal epitope of residues 52-61, but rather is quite heterogeneous, encompassing much of the 46-61 sequence. Further characterization using a panel of T cell hybridoma clones revealed T cell recognition of diverse minimal epitopes within this region. Interestingly, these T hybridomas could be grouped into three distinct categories based on the ability to respond to peptides with or without the native arginine residue at position 61 (61-required, 61-inhibitory, dual responders). Using analogue peptides containing single amino acid substitutions at position 61, further heterogeneity within these hybridoma groups was identified, suggesting the presence of an extremely diverse T cell repertoire for the epitope region. The charge and/or size of the C-terminal residue appears to be a critical factor for certain clones; replacement of the native arginine residue with aspartic acid or glutamic acid enabled a nonstimulatory ligand to specifically antagonize a T cell hybridoma response. Collectively, these results strongly suggest that the C-terminal residue of the predominant epitope in high responder mice plays a critical role in T cell diversity and activation.

Amino Acid Sequence↗
PubMed2003

Evaluation of the appropriateness of pacemaker mode selection in bradycardia pacing: how closely are the ACC/AHA guidelines followed?

Although guidelines for selection of the appropriate pacing mode have been published, little data is available on how closely these are followed in the clinical setting. All 738 patients (men 412, women 326; age 73.4 +/- 0.46 years; range 19-101 years) who underwent pacemaker implantation from 1996 to 2000 were reviewed to determine if the appropriate mode was selected based on the ACC/AHA guidelines with the data collected prospectively. Demographic, investigational, and implantation data including the presence of sinus disease and/or atrioventricular block, diagnosis, indication for pacing, ACC/AHA class indication for device therapy, recommended ACC/AHA mode, implanted mode, and reason for not using the recommended mode were entered into an SPSS data base. Of 738 patients, 708 were cross-tabulated for a match to the guidelines of which 358 (50.6%) had a mode selected that did not conform. The reasons were advanced physical disability (16%), physician choice without identifiable reason (21%), rate modulation selected without identifiable indication (16%), DDD implanted instead of VDD (25%), advanced age (9%), rare need for pacing (6%), a need for specific device features (5%), and unstable stimulation thresholds or difficult venous access (2%). In the treatment of bradyarrhythmias, deviation from the ACC/AHA indicated mode occurred in a substantial proportion of pacing system implantations. However, in many, the deviation appeared appropriate considering the patient's clinical status. Nevertheless, in a smaller proportion of patients the deviation appeared inappropriate requiring rectification. The two outstanding categories were: (1) elderly denied a dual chamber system with no clinical explanation and (2) selection of rate-modulated devices without any indication of chronotropic incompetence.

Aged↗
PubMed1990

Diurnal variation of serum progesterone, but not relaxin, prolactin, or estradiol-17 beta in the pregnant bitch.

The concentrations of progesterone (P), relaxin (Rlx), estradiol (E2) and PRL were measured by specific RIAs in serum samples collected twice daily at 8:00 am and 3:00 pm at weekly intervals after mating and until whelping in five Labrador Retriever bitches. From weeks 3 to 6 of pregnancy, P exhibited a conspicuous and statistically significant diurnal pattern (P less than 0.05), its serum concentration being approximately twice as high at 8:00 am as at 3:00 pm. A similar but nonsignificant trend was observed weeks 2, 7, and 8, and the overall ratio of the am/pm P concentrations was 2.4 +/- 0.28 (P less than 0.001). Rlx, E2, and PRL did not show a diurnal pattern at any time during pregnancy. The glandular sources and regulation of secretion of Rlx were further investigated. Rlx bioactivity was detected in canine placentas and ovaries, providing supportive evidence that these organs may be a dual source of the hormone in canine pregnancy. Injection of ovine PRL in three pseudopregnant bitches significantly increased serum P concentration as compared with seven untreated pseudopregnant controls, but Rlx was not detectable in serum before, during or after PRL treatment. The data support the view that Rlx and P are independently regulated in the bitch; PRL may be a regulator of P, but not of Rlx secretion. However, as PRL showed no diurnal changes in concentration, it does not appear to be directly responsible for the diurnal pattern exhibited by P.

Animals↗
PubMed2005

[Spanish implantable cardioverter-defibrillator registry. First official report of the spanish society of cardiology working group on implantable cardioverter-defibrillators (2002-2004)].

OBJECTIVE: To report the 2002-2004 findings of the Spanish National Implantable Cardioverter-Defibrillator (ICD) Registry, established by the Spanish Society of Cardiology Working Group on Implantable Cardioverter-Defibrillators. MATERIAL AND METHOD: Data were collected prospectively after implantation using a single-page questionnaire returned to the Spanish Society of Cardiology. Participation was voluntary. RESULTS: The registry received reports on 925, 1,046 and 1414 implants, respectively, in the years 2002, 2003 and 2004. These figures represent 63%, 59% and 67.5%, respectively, of the total number of ICDs implanted. The reported implantation rates were 22, 24 and 33 per million, respectively, and the estimated total implantation rates were 35, 41 and 49, per million, respectively. The number of device replacements increased from 20% to 30% between 2002 and 2004. The majority of patients were male, their median age was 66 years, they had severe or moderate left ventricular dysfunction, and they were in functional class I or II. The most common underlying heart disease was ischemic heart disease. The main indications for an ICD were sustained monomorphic ventricular tachycardia and aborted sudden cardiac death, though the number of prophylactic indications has increased. Most ICDs were implanted in an electrophysiology laboratory by a cardiac electrophysiologist. The implantation rates of dual-chamber ICDs and ICDs with cardiac resynchronization therapy were approximately 30% and 15%, respectively. Very few complications occurred during implantation. CONCLUSIONS: The Spanish National ICD Registry contains a representative sample of ICD implantations performed in the country. The registry is one of the largest reported.

Adolescent↗
PubMed2001

Interval cancer peer review in East Anglia: implications for monitoring doctors as well as the NHS breast screening programme.

AIM: To devise a method for reviewing interval cancers that will both educate radiologists and facilitate improvement of breast screening practice. To evaluate different methods for case classification to find one that best serves this purpose. METHOD: The method of peer review and the means by which interval cancers are classified is described. The way in which cases are designated false-negative is an issue of acceptability for radiologists, and so three different methods are evaluated. Each is applied to the data set collected in this region over a 3-year period. RESULTS: For cases read by five readers, when a consensus method was used for classifying cases, the proportion of cases classified as false-negative was 14%. Using a method in which only one of the five readers had to classify a case as false-negative for it to be categorized as such, the proportion of false-negative cases rose to a maximum of 38%. The minimum proportion of cases that could be considered to be false-negative was 6% and was obtained when all five readers had to classify a case as false-negative for it to be so categorized. Consistent with its majority viewpoint, the consensus method gave results for proportions of total cases classified as false-negative which were similar to those given by methods in which cases are classified as false-negative if either three of five readers, or at least 60% of readers, classified it as such. CONCLUSION: For the peer review method to achieve its dual aims of educating radiologists and auditing performance, the participating radiologists must share ownership of the results and view the analysis as fair. The method used to classify interval cancers as false-negative will influence the number so classified. A consensus method has been found to give a result that is both fair and acceptable to our radiologist. Using this method 16% of all reviewed cases were classified as false-negative and 60% as true interval cancers. Britton, P. D. (2001). Clinical Radiology56, 44-49.

Breast Neoplasms↗