Feasibility of using administrative data to compare hospital performance in the EU.

OBJECTIVE: To describe hospitals' organizational arrangements relevant to the abstraction of administrative data, to report on the completeness of administrative data collected and to assess associations between organizational arrangements and completeness of data submission. DESIGN: A cross-sectional STUDY DESIGN: utilizing administrative data. SETTING AND PARTICIPANTS: Randomly selected hospitals from seven European countries (The Czech Republic, France, Germany, Poland, Portugal, Spain, and Turkey). MAIN OUTCOME MEASURES: Completeness of data submission for four quality indicators: mortality after acute myocardial infarction, stroke and hip fractures and complications after normal delivery. RESULTS: In general, hospitals were able to produce data on the four indicators required for this research study. A substantial proportion had missing data on one or more data items. The proportion of hospitals that was able to produce more detailed indicators of relevance for quality monitoring and improvement was low and ranged from 40.1% for thrombolysis performed on patients with acute ischemic stroke to 63.8% for hip-fracture operations performed within 48 h after admission for patients aged 65 or older. National factors were strong predictors of data completeness on the studied indicators. CONCLUSIONS: At present, hospital administrative databases do not seem to be an appropriate source of information for comparison of hospital performance across the countries of the EU. However, given that this is a dynamic field, changes to administrative databases may make this possible in the near future. Such changes could be accelerated by an in-depth comparative analysis of the issues of using administrative data for comparisons of hospital performances in EU countries.

Pseudothrombocytopenia in a neonate due to mother?

UNLABELLED: Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP) is the phenomenon of a false low platelet count reported by an automated haematology analyzer due to in vitro aggregation of platelets. This aggregation is due to the interaction between antibodies and EDTA-dependent crypt antigens on platelets. We observed a new born child whose mother was diagnosed with transient PTCP due to transplacental transmission of maternal immunoglobulin G antibodies during pregnancy. CONCLUSION: Although maternal-neonatal PTCP is rare, it is important to consider this phenomenon as a cause of trombocytopenia, as it can result in unnecessary diagnostic workup and treatment.

Global acetylation and methylation changes predict papillary urothelial neoplasia of low malignant potential recurrence: a quantitative analysis.

Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of this study is to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP, the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being -5% in non-recurrent PUNLMP, -15% in recurrent PUNLMP and -24% in UC. Concerning methylation, there is a slight increase in non-recurrent PUNLMP (+5%), a decrease in recurrent PUNLMP (-19%) followed by a sharp rise for the UC (+61%). In conclusion, there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.

Particle arrangements in proplastids of Triticum vulgare L. seedlings.

Particles having ribosome-like characteristics are described in proplastids of dark-grown wheat seedlings as the membranes of the prolamellar body become transformed, under the influence of light, into grana and fret membranes. Three arrangements of particles were noted: (1) a random distribution of discrete particles; (2) particles occurring in helices or parallel rows; and (3) particles arranged in rough squares with six to eight particles per side. It is possible that the third type of particle is a cross-section of long parallel rods. A particle ranges in size from 170 to 220 A, those of group three being somewhat smaller. The particulates vary from diamond shaped with smooth surfaces to circular with irregular surfaces. These particles have the characteristics of ribosomes as visualized by the electron microscope: they are preserved by glutaraldehyde and osmium tetroxide, they stain intensely with uranyl acetate, and are digested by RNase. Their properties do not coincide with those of viruses, smog-induced particles, stromacenter particles, or phytoferritin. They are frequently adjacent to membranes but never attached to membranes. The involvement of ribosomes in membrane development is discussed.

Degradation of the drug diclofenac in water by sonolysis in presence of catalysts.

Diclofenac, as one of the most popular antiphlogistics, is produced in great quantities. Nowadays this drug is ubiquitously present in the aquatic environment due to its resistance to biodegradation. Degradation by ultrasonic irradiation is a possibility to eliminate diclofenac from water without the addition of chemicals. The sonolysis of diclofenac in water was investigated at ultrasound frequencies of 24 kHz, 216 kHz, 617 kHz, and 850 kHz and in the presence of various catalysts (TiO2, SiO2, SnO2, and titanosilicate). The degradation of diclofenac by sonolysis of an aqueous solution at 617 kHz followed first-order kinetics. Catalysts, especially TiO2 increased the rate of degradation. Within 30 min of irradiation, the relative concentration of diclofenac decreased from 100% to 16%. By HPLC and GC-MS methods, chlorinated anilines, phenols and carboxylic acid derivatives were detected as a result of the sonolysis. About 35% of organic chlorine was transformed into inorganic chloride. Most of the identified degradation products in the sonolysis of diclofenac were the same compounds that were detected during photo-oxidation experiments with this anti-inflammatory drug.

Naturally acquired antibodies to Bacillus anthracis protective antigen in vultures of southern Africa.

Sera from 19 wild caught vultures in northern Namibia and 15 (12 wild caught and three captive bred but with minimal histories) in North West Province, South Africa, were examined by an enzyme-linked immunosorbent assay (ELISA) for antibodies to the Bacillus anthracis toxin protective antigen (PA). As assessed from the baseline established with a control group of ten captive reared vultures with well-documented histories, elevated titres were found in 12 of the 19 (63%) wild caught Namibian birds as compared with none of the 15 South African ones. There was a highly significant difference between the Namibian group as a whole and the other groups (P < 0.001) and no significant difference between the South African and control groups (P > 0.05). Numbers in the Namibian group were too small to determine any significances in species-, sex- or age-related differences within the raw data showing elevated titres in four out of six Cape Vultures, Gyps coprotheres, six out of ten White-backed Vultures, Gyps africanus, and one out of three Lappet-faced Vultures, Aegypius tracheliotus, or in five of six males versus three of seven females, and ten of 15 adults versus one of four juveniles. The results are in line with the available data on the incidence of anthrax in northern Namibia and South Africa and the likely contact of the vultures tested with anthrax carcasses. It is not known whether elevated titre indicates infection per se in vultures or absorption of incompletely digested epitopes of the toxin or both. The results are discussed in relation to distances travelled by vultures as determined by new tracking techniques, how serology can reveal anthrax activity in an area and the issue of the role of vultures in transmission of anthrax.

The pharmacokinetics of meloxicam in vultures.

Vulture populations across the Asian subcontinent have declined dramatically in the last 15 years and are now on the verge of extinction. Although the cause of the population decline was initially unknown, the decrease has recently been conclusively linked to the use of the nonsteroidal anti-inflammatory drug diclofenac in cattle that inadvertently ended up in the vulture food chain. With the vulture numbers continuing to decline by up to 48% a year, the Indian, Nepali and Pakistan governments have recently banned the manufacture and importation of veterinary diclofenac. They have also suggested meloxicam as an alternate anti-inflammatory for use in cattle. This recommendation was based on extensive acute safety studies in the African White-backed vulture (Gyps africanus), which evaluated worst case scenarios of maximum intake based on a once in three day feeding pattern. However, the possible cumulative pharmacokinetic and pharmacodynamic effects in vultures receiving multiple daily doses of meloxicam over time were not assessed. At present very little pharmacokinetic or pharmacodynamic information is available to add further support for the safety of meloxicam in this animal species. This article discusses the oral and intramuscular pharmacokinetics of meloxicam in Cape Griffon vultures (Gyps coprotheres). Therapeutic drug monitoring was also undertaken in White-backed, Egyptian (Neophron pernopterus) and one Lappet Faced vulture (Torgos tracheliotos). In all these species, meloxicam was characterized by a short half-life of elimination. The rapid metabolism of meloxicam in combination with a short duration of effect in the studied species Gyps vultures shown in this study makes it unlikely that the drug could accumulate. This confirms the safety of repeated exposure to meloxicam in vultures of this genus.

A clarification for the subgenera of Paramacrobiotus Guidetti, Schill, Bertolani, Dandekar and Wolf, 2009, with respect to the International Code of Zoological Nomenclature.

The recent re-description of Paramacrobiotus Guidetti, Schill, Bertolani, Dandekar and Wolf, 2009 has inadvertently led to the description of an objective synonym within its subgenera nominal taxa. To resolve this issue, we have re-described both subgenera, and proposed a new substitute name for one subgenus, in line with the International Code of Zoological Nomenclature. Additionally we have confirmed the placement of two recently published Paramacrobiotus species, not included in the last revision, within the respective subgenera established herein.

Karyometric marker features in normal-appearing glands adjacent to human colonic adenocarcinoma.

The expression of nuclear marker features in normal-appearing tissue adjacent to colonic adenocarcinoma was investigated. Formalin-fixed, paraffin-embedded tissue sections of colon from 9 patients with adenocarcinoma and from 9 normal controls were cut 4 microns thick, Feulgen stained, and measured by a cell image analysis system using a Matrox MVP-AT/NP imaging board. Thirty nuclei in the tumor region, 30 nuclei 2 mm into the histologically normal-appearing distal margin, and the same number at 5, 10, 20, and 50 mm into the margin were measured for each patient. An additional 30 nuclei were recorded from 9 patients each free from colonic disease. Nuclear features were selected to discriminate between tumor nuclei and nuclei from normal control subjects and between nuclei measured in the histologically normal-appearing margin next to the tumor and control nuclei. Eight micromorphometric measures were found to be statistically significantly different in nuclei measured in the margin site, including features describing staining density (total absorbance, average absorbance 20% below mean, average absorbance 20% above mean) chromatin texture (cooccurrence matrix, run length, and peripheral tendency) and nuclear area. The category differences are statistically highly significant.

Thyroid hormone-induced changes in gluconeogenesis and ketogenesis in perfused rat liver.

The regulation of ketogenesis and gluconeogenesis was studied in isolated, perfused livers from hyper- and euthyroid rats. Experimental conditions were varied with respect to lactate and fatty acid concentration in the perfusion medium and with respect to the nutritional state of the rats. 1. The rate of uptake of oleate in perfused livers was independent of the thyroid and nutritional states of the animals. 2. In livers from 48-h-fasted rats no difference was found in rates of ketogenesis between the euthyroid and hyperthyroid livers except when 10 mM lactate was present in the perfusate. In recently fed rats the rates of ketogenesis from oleate (1 mM) and endogenous substrates were low in euthyroid livers (0.45 and 0.05 mumol/min per g liver, respectively), while these rates in hyperthyroid livers were (1.333 and 0.136 mumol/min per g liver, respectively). With octanoate as substrate, high rates of ketogenesis were found in recently fed livers from both euthyroid and hyperthyroid rats (1.573 and 1.717 mumol/min per g liver, respectively). 3. Without oleate in the perfusion medium the rate of gluconeogenesis from low (1 mM) lactate concentrations in livers from 48 h-fasted-rats was slightly increased in the hyperthyroid state (0.548 mumol/min per g liver) compared to the euthyroid state (0.408 mumol/min per g liver). When lactate concentration in the perfusion medium was raised to 10 mM the rate of gluconeogenesis was increased 4-fold in the hyperthyroid livers (1.800 mumol/min per g liver) but only 20% in the euthyroid livers (0.490 mumol/min per g liver). The presence of oleate (1 mM) had no effect on the rate of gluconeogenesis from low lactate concentrations in livers form 48-h-fasted animals of either thyroid state. At 10 mM lactate the inclusion of oleate caused a pronounced stimulation of gluconeogenesis in euthyroid livers (from 0.490 to 1.766 mumol/min per g liver) but not in hyperthyroid livers (from 1.800 to 1.973 mumol/min per g liver) so that the difference in the rate of gluconeogenesis between the two thyroid states disappeared. 4. The content of endogenous substrates was measured in liver biopsies taken before perfusion. The glycogen concentration was independent of the thyroid state in 48-h fasted animals. The triglyceride content was independent of the thyroid state in recently fed animals. In recently fed animals the glycogen content was reduced by 90% in hyperthyroid animals, and in 48-h-fasted animals the triglyceride content was reduced by 50% in hyperthyroid animals. 5. The energy cost of gluconeogenesis from lactate appeared to be independent of the thyroid state.

Rapid in vitro assay for predicting response to fluorouracil in patients with metastatic breast cancer.

PURPOSE: To determine if a rapid 3H-uridine uptake assay using breast tumor cells from biopsy specimens could predict clinical response to fluorouracil (5FU) in patients with metastatic breast cancer. PATIENTS AND METHODS: A double-blind prospective study was conducted of 60 patients with measurable, metastatic breast cancer who had failed to respond to at least one prior chemotherapy regimen. Patients received 5FU 300 mg/m2/d by continuous infusion and were monitored for response. Tumor cells from biopsy specimens were grown in microwells and exposed for 3 days to 0.1, 1.0, 10.0, and 100.00 micrograms/mL of 5FU on strips coated with drug and extracellular matrix. Cells were pulsed with 3H-uridine overnight. Incorporated radioactivity was compared for wells with and without drug. Results were available 4 days from specimen submission. RESULTS: Of 45 eligible patients, 11 (24%) were not assessable in vitro. Nine patients were assessable in vitro, but not clinically. Of the remaining 25 patients, who were assessable both clinically and in vitro, there was one complete response (CR), five partial responses (PRs), five cases of stable disease, and 14 cases of progressive disease, for an objective response rate of 24%. Response in vitro was significantly correlated with clinical response (P = .002). Of six clinical responders, five also responded in vitro, for an assay sensitivity of 83%. Of 19 nonresponders, 17 were nonresponders in vitro, for a specificity of 89%. The positive predictive value of the test was 71% (five of seven), and the negative predictive value was 94% (17 of 18). CONCLUSION: Results of an in vitro assay were significantly correlated with clinical response in patients with metastatic breast cancer treated with continuous infusion 5FU.

Karyometry in the early detection and chemoprevention of intraepithelial lesions.

The ideal chemopreventive agent targets pre-neoplastic changes and intraepithelial neoplasia, preventing progression over time without notable side effects. Assessment of success of chemopreventive intervention in the short and medium term remains a challenge, and in this review the suggestion is investigated that karyometric measurements constitute suitable markers of chemopreventive efficacy. Karyometry provides the sensitivity required to detect small differences amidst relatively high biological variability. It can help establish progression curves of intraepithelial neoplasia (IEN) to invasive cancer, and thus detect chemopreventive effects. Such effects can be observed in two ways, at the group level (intervention vs. placebo), and at the case (or patient) level. The latter is more difficult to establish, necessitating the development of specialised statistical methods. Analysis of between-case and within-case heterogeneity can reveal useful information about cancer progression and prevention. We suggest that karyometry can objectively quantify IEN progression, providing a framework for statistically securing chemopreventive effects. It can act as an integrating biomarker by detecting chemopreventive activity even when the mechanism for a given progression pathway is unknown, or when multiple pathways exist. The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size.

Effects of verapamil on diurnal and thyrotropin-releasing hormone-stimulated prolactin levels in man.

The effects of the calcium entry blocker verapamil on the 24-h profile of PRL secretion and on the PRL response to TRH were investigated in six healthy volunteers. Verapamil (120 mg, three times daily) was administered orally for 1 week. In all subjects both basal and TRH-stimulated PRL levels were markedly elevated by verapamil. The average diurnal PRL concentration was increased from 13.0 +/- 2.0 micrograms/L to 25.2 +/- 4.4 (mean +/- SE; P = 0.02). Diurnal rhythm and pulsatility of PRL secretion were seen both before and during verapamil administration. Mean peak PRL concentrations after TRH injection (200 micrograms, iv) were significantly increased from 72.6 +/- 11.6 to 115.2 +/- 16.8 (P less than 0.01), and the mean area under the PRL concentration-time curves from 4332 +/- 962 micrograms/L.120 min to 6975 +/- 1334 (P = 0.01). The data are in striking contrast with previous findings from in vitro studies where verapamil has been reported to block calcium-mediated stimulus-secretion coupling and inhibit hormone secretion from pituitary cells. Interference with other PRL-regulating mechanisms may account for the demonstrated verapamil-induced PRL secretion in vivo.

Quantitative morphology of late renal radiation injury.

Late radiation injury manifests itself in all morphologic compartments of the kidney, but loss of cell mass is most significant in the proximal convoluted tubules. Development of an end stage or nonfunctional kidney requires 12 or more months after single fraction X ray exposures of about 12 Gy (2, 5, 13) and is associated with marked morphologic alterations of renal tubules. Radiation induced changes were studied at 6 months after irradiation, a time interval when histological alterations appear minor, but in previous studies were shown to correlate with the later end stage alterations (5, 8, 9). Renal alterations were graded objectively based on renal weight, variation in size of tubule cell nuclei, and glomerular nuclear volume fraction. Irradiation was associated with loss of renal weight, increased variability of tubule nuclear size, and previously unappreciated changes in glomerular nuclear volume fraction. A classification index derived from a weighted combination of renal weight ratio and tubule cell nuclear variability correlates with radiation dose and with previously established subjective histologic grading of renal damage, and allows objective comparisons of various fractionation schedules.

Ultrafast laser scanner microscope.

Advances in monolayer deposition of cervical cells have removed one of the last serious obstacles to the design of high-resolution automated diagnostic assessment systems. In this article, we describe the design considerations for a system that is capable of acquiring, within 60 sec, a 0.5 micron digitized image of a 4 cm2 area on a standard glass slide. The most feasible approach is found to be a system using a rotating polygon to sweep the focused spot from a laser across a 2-mm scan line while the slide is uniformly translated perpendicular to the scan direction the use of laser sources (a helium-neon laser at 632 nm and a krypton ion laser at 568 and/or 476 nm) as compared to the incoherent light sources used in conventional microscope systems alleviates many of the optical design problems and provides the proper wavelengths needed for recognition of Papanicolaou stained cells. We also find that focus control of the scanning spot should be achievable using a technique involving a holographic grating. Other relevant considerations such as sample heating problems, multiphoton absorption by the sample, detector signal-to-noise ratios, laser amplitude noise control, and the digitization and buffering of the data stream are also discussed.

Subacute thyroiditis (de Quervain) presenting as a painless "cold" nodule.

A 49-yr-old woman presented with a solid, painless, nontender nodule in the left thyroid lobe. Thyroid scintigraphy revealed a solitary "cold" area in the left lobe and a slightly decreased 24-hr radioactive iodine thyroid uptake (9%). Although there were no specific clinical or biochemical signs suggesting thyroiditis needle aspiration cytology showed the presence of a subacute thyroiditis. Approximately 1 mo later the entire thyroid gland was affected leading to a completely suppressed thyroid radioiodine uptake and elevated serum thyroid hormone concentrations. This case illustrates that in the early phase of the disease, subacute thyroiditis may present as a solitary, painless, "cold" nodule and should be considered in the differential diagnosis of such lesions.

Atypical adenomatous hyperplasia (adenosis) of the prostate: development of a Bayesian belief network for its distinction from well-differentiated adenocarcinoma.

The diagnosis of atypical adenomatous hyperplasia (AAH) of the prostate and its distinction from well-differentiated prostatic adenocarcinoma with small acinar pattern (PACsmac; Gleason primary grades 1 or 2) are affected by uncertainties that arise from the fact that the knowledge of AAH histopathology is expressed in descriptive linguistic terms, words, and concepts. A Bayesian belief network (BBN) was used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependencies between elements in the reasoning sequence. A shallow network was designed and developed with an open-tree topology, consisting of a root node containing two diagnostic alternatives (eg, AAH v PACsmac) and 12 first-level descendant nodes for the diagnostic features. Eight of these nodes were based on cell features, three on the type of gland lumen contents and one on the gland shape. The results obtained with prototypes of relative likelihood ratios showed that belief for the diagnostic alternatives is high and that the network can differentiate AAH from PACsmac with certainty. The features that best contributed to the highest belief were those concerning the nucleolar size, frequency, and location. In particular, after the analysis of five nucleolar features (prominent nucleoli, inconspicuous nucleoli, nucleoli with diameter greater than 2.5 micron, nucleolar margination, and nuclei with multiple nucleoli), the belief for AAH was 1.0, being already close to 1.0 when three were evaluated (the value range is 0.0 to 1.0; the closer to 1.0, the greater the belief). The contribution of the three features concerning the gland lumen contents (mucinous material, corpora amylacea, and crystalloids) was such that the final belief did not exceed 0.8. Results with the group of remaining features (eg, basal cell recognition, gland shape variation, cytoplasm appearance, and nuclear size variation) were slightly better. These features allowed a substantial accumulation of belief that was already greater than 0.9 when three were polled. However, the maximum belief value was never obtained. In conclusion, a BBN for AAH diagnosis offers a descriptive classifier that is readily implemented, and allows the use of linguistic, fuzzy variables, and the accumulation of evidence presented by diagnostic clues.

Computer analysis of defined populations of lymphocytes irradiated in vitro. III. Evaluation of human T and B cells of peripheral blood origin.

The radiosensitivities of lymphocytes of peripheral blood origin obtained from two healthy 45 year old male donors were studied simultaneously at yearly intervals over a three year period. Hypaque-Ficoll purified cells were exposed in vitro to 0, 5, 50, and 500 rads and then evaluated serially for viability of T and B cells, responsiveness to PHA and Con A, and morphologic evidence of injury as documented by standard light microscopy and computer assisted morphometric analysis. The results showed that T cells in both subjects were less radiosensitive than B cells. Differences between the two subjects also existed in the radiosensitivity of these two subpopulations of lymphocytes, differences that remained constant over the three years period of observation. The differences correlated with similar discrepancies in mitogenic responsiveness and are thought to relate to variations in the relative proportions of subpopulations of T and B cells. In the mouse, T and B cell subpopulations differ in radiosensitivity. The data reported herein are consistent with a similar situation in man.

Computerized diagnostic decision support system for the classification of preinvasive cervical squamous lesions.

Previous studies have revealed considerable interobserver and intraobserver variation in the histological classification of preinvasive cervical squamous lesions. The aim of the present study was to develop a decision support system (DSS) for the histological interpretation of these lesions. Knowledge and uncertainty were represented in the form of a Bayesian belief network that permitted the storage of diagnostic knowledge and, for a given case, the collection of evidence in a cumulative manner that provided a final probability for the possible diagnostic outcomes. The network comprised 8 diagnostic histological features (evidence nodes) that were each independently linked to the diagnosis (decision node) by a conditional probability matrix. Diagnostic outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III. For each evidence feature, a set of images was recorded that represented the full spectrum of change for that feature. The system was designed to be interactive in that the histopathologist was prompted to enter evidence into the network via a specifically designed graphical user interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions were used to derive the relative likelihoods for the alternative feature outcomes, the likelihood vector was entered into the network, and the updated diagnostic belief was computed for the diagnostic outcomes and displayed. A cumulative probability graph was generated throughout the diagnostic process and presented on screen. The network was tested on 50 cervical colposcopic biopsy specimens, comprising 10 cases each of normal, koilocytosis, CIN I, CIN II, and CIN III. These had been preselected by a consultant gynecological pathologist. Using conventional morphological assessment, the cases were classified on 2 separate occasions by 2 consultant and 2 junior pathologists. The cases were also then classified using the DSS on 2 occasions by the 4 pathologists and by 2 medical students with no experience in cervical histology. Interobserver and intraobserver agreement using morphology and using the DSS was calculated with kappa statistics. Intraobserver reproducibility using conventional unaided diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall reproducibility between individuals. Using the DSS, however, did not enhance the diagnostic performance of junior pathologists when comparing their DSS-based diagnosis against an experienced consultant. However, the generation of a cumulative probability graph also allowed a comparison of individual performance, how individual features were assessed in the same case, and how this contributed to diagnostic disagreement between individuals. Diagnostic features such as nuclear pleomorphism were shown to be particularly problematic and poorly reproducible. DSSs such as this therefore not only have a role to play in enhancing decision making but also in the study of diagnostic protocol, education, self-assessment, and quality control.

The diagnostic pattern in histopathology.

Defining in precise detail the diagnostic clues used by histopathologists to arrive at a diagnosis is a difficult process; however, better analytic understanding of this process is a prerequisite for the design of diagnostic expert systems. Such systems offer the potential for consistency and setting standards in the diagnostic evaluation of difficult situations. Diagnostic clues as offered by the image represent two-dimensional information. Their description is entered into the knowledge base of an aspect system, however, in the form of a description, which is one-dimensional. Preserving all of the two-dimensional dependence structure in this conversion is a fundamental problem. Use of the description to generate simulated imagery tests whether or not the two-dimensional dependence structure of a given tissue architecture has been adequately represented in the analytic description. This analytic description would then be entered into the knowledge base of an expert system.