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PubMed1996

Optimization of factors affecting the state of normality of a medical image.

The purpose of this paper is to examine the first stage of the diagnostic process in medical imaging, namely determination of the state of normality, and to attempt to optimize factors contributing to this stage. An image of a given type is defined as abnormal if it does not belong to the appropriate class of normal images. All images must be pre-processed involving image registration and normalization to align and scale the images with respect to each other. Normal ranges may be determined for each voxel (or other appropriate region) from a representative normal sample using univariate analysis, obtaining mean and standard deviation images, or multivariate analysis, which accounts also for normal patterns of variation (represented as principal components). For a new image, the variation from normality (in SDs) for each region may be determined. Since the spatial distribution of this parameter is thought to be relevant, connectivity of abnormal voxels was considered as a possible factor. For the purposes of this study, SPECT images indicating regional cerebral blood flow were used. Images from 50 normal subjects formed the normal sample. A further 40 normal subjects and 200 patients referred with suspected dementia were then analyzed using the normal ranges. ROC analysis, using number of SDs as a variable threshold, was used to optimize the factors. Normalization to global values followed by multivariate analysis using four or five principal components provided optimal discrimination. Connectivity of voxels emerged as an important factor, around 10 connected voxels being optimal for this study.

Adolescent↗
PubMed2026

Role of IFIT1 and IFIT3 in systemic lupus erythematosus: modeling a diagnosis and exploring immune regulation.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by multi-organ involvement and a protracted clinical course. Current diagnostic strategies, which rely heavily on clinical symptoms and serology, are often insufficient for early detection. Therefore, highly accurate diagnostic biomarkers are urgently needed to facilitate early intervention and optimize personalized treatment strategies. D atasets GSE61635 and GSE135779 were integrated to identify differentially expressed genes. Weighted gene co-expression network analysis (WGCNA) was performed to isolate the module with the strongest clinical relevance. Mendelian randomization and single‑cell RNA‑seq were used to identify key disease‑relevant genes. A diagnostic model was then constructed, and gene set variation analysis (GSVA), along with gene set enrichment analysis (GSEA), was conducted to elucidate the underlying molecular pathways. IFIT1 and IFIT3 were identified as 2 core genes highly expressed in monocytes and T cells of SLE patients. Functional enrichment analysis revealed that these genes were enriched in immune-related pathways, metabolic pathways related to inflammation and genomic stability. The diagnostic model showed good accuracy, with an area under the curve (AUC) of 0.974 on the training set and 0.912 on the validation set. IFIT1 and IFIT3 represent promising biomarkers for diagnosing SLE and appear to mediate key immune and metabolic disturbances. Furthermore, the developed model serves as an accurate and reliable instrument for early diagnosis and personalized therapy. Large-scale clinical studies are warranted to further validate these findings and evaluate their clinical application.

Humans↗
PubMed1993

[Diagnosis of recurrent intervertebral disk prolapse with nuclear magnetic resonance tomography].

Persisting low back pain after lumbar discectomy may have many reasons. Reoperation is likely to be successful if a recurrent disc prolapse is found. The sensitivity and validity of diagnostic tools used cannot as yet be considered to be optimal. For this reason in our study 130 patients who were supposed to have a recurrent disc herniation underwent MRI with and without application of Gadolinium DTPA. In all patients we saw enhancement in the spinal canal. Sensitivity of MRI as verified by reoperation was > 90%. Hence, we can recommend this diagnostic tool for the diagnosis of recurrent disc herniation.

Adult↗
PubMedDate not supplied

[Optimizing resources in nuclear cardiology].

Myocardial perfusion SPECT imaging (MPI) provides substantial diagnostic and prognostic information in patients with known or suspected coronary artery disease (CAD). Furthermore, it has been demonstrated that the application of MPI results is a cost-effective modification of patient management. Several studies have demonstrated that a chest pain center (CPC) using MPI significantly reduce the number of patients hospitalized from the emergency department for further evaluation of chest pain, and restricted hospitalization to more appropriate patients. However, time-consuming and costs of MPI studies might represent a significant issue for patients and nuclear laboratory logistics. We addressed the question whether in patients evaluated for CAD stress with only MPI might reduce costs and time without loosing the efficacy for detecting CAD. We included a consecutive series of 122 patients. All patients underwent stress-only Tc99m sestamibi MPI. The study population was divided into two groups: group I consisted of 26 patients with stress-only abnormal MPI and group 2 consisted of 96 patients with stress-only normal MPI. All group I patients underwent angiography and showed a significant lesion in at least one vessel in 22 patients. Mean follow-up of group II patients was 12.65 +/- 2.83 months and the overall cardiac event rate was 0.2%. Stress-only MPI was completed in a shorter period of time than reststress MPI (57 +/- 5.95 vs 180 +/- 2 minutes, p < 0.000.1). In addition, stress-only MPI studies saved 40% of costs. We concluded that in patients with low to medium pretest probability for CAD, stress-only MPI results in a safety strategy that improves cost-efficiency and decreases demand on nuclear laboratory time.

Coronary Artery Disease↗
PubMed2001

Diagnostic orthotics to establish the functional mandibular-maxillary relationship for orthodontic corrections.

Under optimal anatomic and physiologic circumstances, there exists a harmonious and functional balance between the occlusion, muscles of mastication and joint relationships referred to as a functional bite relationship. A diagnosis and treatment to the habitual bite relationship is provided if the function of the joints, muscles and associated structures is determined to be normal. If compromises of form or function are determined, a diagnostic orthotic is an essential tool to evaluate why the habitual bite position is not the best functional bite position and to also help determine a better functional relationship to avoid tissue and system compromise. The benefit of the diagnostic orthotic is the ability to establish an arbitrary reversible diagnostic relationship, evaluate the tissue and system response to this new association over time, and determine if the new treatment position is better for the patient than the habitual bite association.

Dental Occlusion↗
PubMedDate not supplied

Atypia in fine needle aspiration cytology of nonpalpable and palpable mammographically detected breast lesions.

Widespread use of fine needle aspiration (FNA) in conjunction with mammography may lead to increased atypical or suspicious cytologic diagnoses. To assess the incidence and cytologic criteria of atypia in a mammographically screened population, we reviewed 220 FNA samples in this diagnostic category (5.8% incidence) from 3,798 FNAs performed in 1990-1991. The atypical category (134 cases) included 72 benign and 62 malignant confirmed cases. Common benign diagnoses were fibroadenoma and fibrocystic changes (33 cases, or 46%). Features responsible for an atypical diagnosis in benign cases were increased cellularity, single epithelial cells and "reactive nuclear atypia," the last defined as a finely granular, uniform chromatin pattern with small, prominent nucleoli. The suspicious category included 86 cases; only 10 cases (12%) were confirmed benign lesions, and the remainder were malignant. These benign cases included 3 fibroadenomas, 3 fibrocystic changes, 3 papillomas and 1 scar after radiotherapy. Two cases had prominent inflammation, a finding that should prompt caution. Malignant diagnoses in both categories included infiltrating and in situ cancers. A combination of limited cellularity, drying and/or bland nuclear features precluded a definitive diagnosis of cancer in many cases. For optimal management of mammographically screened patients, an acceptable "atypical" diagnostic rate should be defined for FNA. We conclude that a rate of less than 5% can be achieved by recognition of the following: (1) reactive atypia in the setting of fibrocystic and fibroadenomatous patterns, (2) significance of atypia in the setting of inflammation, and (3) improved sampling and sample preparation.

Adult↗
PubMed2006

[Optimized RT-PCR based detection of specific genetic abnormalities within malignant hematopoietic disorders].

The moleculargenetic detection of specific genetic abnormalities within malignant hematopoietic disorders is an important diagnostic tool with relevance for the differential diagnosis, therapy and prognosis.According to a modified and optimized RT-PCR based technique native bone marrow aspirates and peripheral blood samples of 183 patients were investigated for the presence of specific genetic abnormalities. The histological diagnosis of all CMLs t(9;22) and variants of AMLs M3 t(15;17) and t(11;17) were moleculargenetically confirmed. Additionally one t(5;12) positive chronic myelomonozytic leukemia, one t(8;21) positive AML M1, one t(9;22) positive B-ALL and in each case one t(6;9) and one t(3;21) positive myelodysplastic syndrome were detected. The hereby described method is a simple, specific and reliable technique for the rapid moleculargenetic detection of specific genetic abnormalities within malignant hematopoietic disorders with implication for the diagnosis/differential diagnosis, prognosis and therapy.

Gene Expression Regulation, Neoplastic↗
PubMed1998

[Clocking diagnostic and therapeutic procedures in coronary care unit patients: analysis of clinical performance times].

BACKGROUND: An optimal use and exploitation of professional personnel is of paramount importance for health management organizations, as human resources are both their greatest asset and heaviest financial burden. To better understand the amount of medic and paramedic work and time required for the typical diagnostic and therapeutic procedures in a coronary-care unit setting, we measured their average times and analyzed their inherent co-factors. METHODS: This study was conducted on 206 consecutive coronary-care unit patients. These patients were divided into subgroups according to their admission diagnosis: acute myocardial infarction, unstable angina, acute cardiac failure, pulmonary embolism or other pathologies. Each subgroup was then subdivided even further according to the severity of their clinical status. Diagnostic and therapeutic procedures ("macroactivities") have been identified and each one was subdivided into sub-procedures ("microactivities"). All microactivities were carefully clocked in every patient in order to calculate the average execution time for every macroactivity. RESULTS: Our data show that myocardial infarction patients and, in general, a more severe clinical status required a longer stay in the coronary-care unit. Again, longer overall clinical performance times were necessary in myocardial infarction patients as compared to the unstable angina subgroup. There were no statistically significant differences among other subgroups. More severely ill patients required longer clinical performance times because of both a longer coronary-care unit stay and longer clinical performance time per day. More than half of the total clinical performance time for each patient was spent during the first two days. Paramedics supplied more than 80% of the total performance time. CONCLUSIONS: The authors undertook a study of typical coronary-care unit clinical activities by clocking the performance times of the usual diagnostic and therapeutic procedures. The data thus obtained come from direct measurements and describe the clinical performance of both medics and paramedics in a real-life setting. This could thus be used as a yardstick to verify current workload standards. It is hoped that a deeper understanding of these activities will optimize the full exploitation of available human resources.

Adult↗
PubMed1997

Cryptosporidiosis in HIV-infected patients: diagnostic sensitivity of stool examination, based on number of specimens submitted.

OBJECTIVES: To determine the optimal number of stool specimens needed for the diagnosis of cryptosporidiosis. METHODS: Four hundred thirty-five admissions were reviewed (291 patients) in which stool specimens were examined for Cryptosporidium parvum oocysts (mean of 1.47 specimens per admission), using a modified acid-fast stain. The diagnostic yield of each specimen was determined. RESULTS: Cryptosporidium parvum oocysts were found in 81 of 435 admissions (18.6%). Ninety-six percent of the positive cases were detected on the first stool specimen analysis, and 100% were detected by the second specimen. CONCLUSIONS: Examination of one specimen is generally appropriate for the diagnosis of cryptosporidiosis in a hospitalized patient with AIDS presenting with diarrhea. Examination of a second specimen may be appropriate if the first specimen is negative and there is a high clinical index of suspicion.

AIDS-Related Opportunistic Infections↗
PubMed2000

Objective assessment of the contribution of each diagnostic test and of the ordering sequence in jaundice caused by pancreatobiliary carcinoma.

BACKGROUND: Computer-assisted diagnostic systems are not substantially more accurate than the clinician in the differential diagnosis of jaundice but may help in optimal selection and sequencing of tests. The present study aimed to assess with an electronic diagnostic tool the pattern of ordering tests and the diagnostic contribution and related financial cost of each test in jaundiced patients with pancreatobiliary carcinoma, in an effort to make the clinician's diagnostic behaviour more efficient and economical. METHODS: Clinical and diagnostic test data were prospectively gathered from 356 jaundiced patients with pancreatobiliary carcinoma and entered in a Bayesian diagnostic programme. The test results were added to the existing diagnostic evidence, and the programme calculated the diagnostic contribution of each test. RESULTS: A total of 1804 diagnostic tests were ordered. Quantitative assessment of the diagnostic contribution of each test showed that percutaneous transhepatic cholangiography and computed tomography were associated with the highest provision of information. The most cost-effective tests were ultrasonography and liver function tests. CONCLUSIONS: It is possible to determine objectively the diagnostic contribution of each test in establishing the diagnosis of pancreatobiliary carcinoma. The observed physician behaviour in ordering the various diagnostic tests might be improved with regard to its efficacy and its cost-effectiveness profile.

Bayes Theorem↗
PubMed2005

Epilepsy in the UK: misdiagnosis, mistreatment, and undertreatment? The Wrexham area epilepsy project.

OBJECTIVE: To assess the diagnostic and therapeutic difficulties in patients with epilepsy who had never come into contact with specialist services. METHODS: Assessment was offered to 676 patients diagnosed as having epilepsy and receiving anti-epileptic drug therapy (AED), who had no previous contact with the local epilepsy services. Two hundred and seventy-five patients gave consent and attended for reassessment. We identified the proportion of patients (a) who had previously seen a neurologist, (b) in whom the diagnosis of epilepsy was not secure, (c) in whom planned AED withdrawal could be considered (d) in whom seizure control could be improved. RESULTS: 53/275 (19.3%) of those attending for review had previously been seen by a neurologist. 87/275 (31.6%) patients ultimately received continued specialist care. Diagnostic doubt was expressed in 3/53 (5.6%) and 42/222 (18.9%) of patients diagnosed by neurologist and non-specialist, respectively. Of 133/219 (60.7%) of patients whose epilepsy was in remission, only 6 elected to withdraw or change medication. Of 18 patients with diagnostic doubt who accepted follow-up, 12 successfully stopped treatment. 17/55 (30.9%) patients with active epilepsy (10 partial, 7 generalised) achieved at least a 1 year remission consequent upon treatment in this clinic. In 15 cases this was a first ever remission. CONCLUSION: Approximately 55% of the population of adults receiving treatment for epilepsy have never received specialist advice. Reassessment of these patients uncovers diagnostic uncertainty, failure to classify (leading to sub-optimal therapy) and lack of information and advice about all aspects of epilepsy care. The development of integrated services for people with epilepsy (PWE) must take account of this hidden need. The new General Medical Services contract for general practitioners will bring this need to our attention, and our experience will help predict the measures required to deal with the under-treatent and mistreatment of this group. The majority of PWE, not currently receiving shared care, merit reassessment and approximately one-third will require continued specialist care. Existing services do not have the capacity to process a marked increase in rate of referral. This project informs prioritisation of referrals and service reorganisation.

Adolescent↗
PubMed1996

Optimal primer selection for clonality assessment by polymerase chain reaction analysis. III. Intermediate and high-grade B-cell neoplasms.

Previous studies have reported that low-grade B-cell lymphoproliferative disorders have variable B-cell monoclonality detection rates by polymerase chain reaction (PCR) analysis. For instance, monoclonal B-cell populations from chronic lymphocytic leukemia/small lymphocytic leukemia and mantle cell lymphoma are most often readily amplified with a single primer pair, whereas follicular lymphomas and plasma cell neoplasms require alternative strategies to approach these higher diagnostic sensitivity standards. Because most published reports have not focused on the variation in PCR B-cell monoclonality detection among subtypes of intermediate and high-grade B-cell neoplasms, additional information is necessary to determine primer selection strategies and identify problematic tumor subtypes within this group. The current investigation, the third part in a series, was aimed at documenting the efficiency of B-cell monoclonality detection by PCR in 71 aggressive B-cell neoplasms of various types using a comprehensive approach. A predetermined panel of primer sets was used in an algorithmic fashion. Specifically, all samples were analyzed with the standard VH-FRIII/JH assay previously shown to have the highest efficiency of monoclonality detection within low-grade B-cell lymphoproliferative disorders. Negative samples were further evaluated with primer sets in the following order until a positive result was observed, or all primer sets were used: (1) bcl-2/JH, (2) VH-FRI family specific/JH, and (3) VH-FRI consensus/JH. Forty-three (61%) of the 71 B-cell neoplasms evaluated with VH-FRIII/JH showed monoclonal B-cell populations. Sequential use of the three reserve primer sets in samples negative with this initial primer pair resulted in an overall improvement in PCR detection from 61% to 82% (58 of 71 specimens) (P < .001). The VH-FRI family specific assay identified B-cell monoclonality in 11 (73%) of these 15 specimens and was the most productive reserve primer set. Individual categories exhibited the following initial (I) and final (F) PCR detection rates: acute lymphoblastic leukemia/lymphoblastic lymphoma, 11 specimens (I = 91% to F = 91%); small noncleaved cell lymphoma, 14 specimens (I = 79% to F = 86% [P > .25]); diffuse large cell lymphoma, 33 specimens (I = 52% to F= 85% [P < .005]) and large cell, immunoblastic lymphoma, 13 specimens (I = 38% to F = 62% [P < .01]). The authors have shown that comprehensive PCR analysis is capable of detecting B-cell monoclonality in a significant proportion of samples from each subtype of intermediate and high-grade B-cell neoplasm. The VH-FRIII/JH assay was an adequate initial primer set, but required augmentation with the reserve PCR assays to attenuate the false negative rate and improve diagnostic sensitivity. The B-cell clonality PCR assay is optimally used as a screening tool and when used in this fashion, the more laborious and time-consuming restriction fragment-Southern blot hybridization (RF-SBH) method for IgH gene rearrangement detection may be limited to a relatively small proportion of PCR-negative aggressive B-cell neoplasms.

Algorithms↗
PubMed2000

Validation and comparison of three brief depression scales in an elderly Chinese population.

The study aimed to establish the diagnostic accuracy of the Geriatric Depression Scale (GDS), the Even Briefer Assessment Scale for Depression (EBAS DEP), and the single question test for depression in our elderly Chinese population, and to determine if any one instrument was to be preferred. Ninety-eight community-living, socially active and non-depressed elderly and 75 patients diagnosed with depression were administered the three depression scales. Receiver operating characteristics (ROC) were employed to determine the optimal cut-off scores for the GDS and EBAS DEP, and the diagnostic performance of all three instruments were then compared. ROC analysis indicated an optimal cut-off score of 4 and above for the 15-item GDS, with a sensitivity of 84.0% and a specificity of 85.7%, while the EBAS DEP had 77.3% sensitivity and 89.8% specificity at the optimal cut-off score of 3 and above. The sensitivity and specificity of the single question were 64.0% and 94.9%, respectively. The non-parametric test of the areas-under-the-curve showed no significant difference between the diagnostic performances of the GDS and the EBAS DEP; visually, however, the ROC plot of the GDS was superior. The GDS, the EBAS DEP, and the single question were all valid screening tools for depression in the elderly Chinese population. For busy physicians, there is rationale to first use the single-question test, supplemented where necessary with either the GDS or the EBAS DEP, as an efficient diagnostic strategy for identifying depression amongst older Chinese patients.

Aged↗
PubMed2005

Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection.

BACKGROUND: This study aimed to evaluate the diagnostic utilities of monocyte HLA-DR as an infection marker in the identification of early-onset clinical infection and pneumonia in newborn infants. METHODS: Term newborns in whom infection was suspected when they were <72 h of age were eligible for enrollment in the study. C-reactive protein (CRP), monocyte HLA-DR and neutrophil CD64 expressions were quantitatively measured at the time of sepsis evaluation (0 h) and 24 h afterwards by flow cytometry and standard laboratory method. RESULTS: A total of 288 infants with suspected sepsis were investigated, and 93 were found to be clinically infected. There were no significant differences in monocyte HLA-DR expression between the infected, non-infected and control groups at 0 h (median (interquartile range): 13,986 (10,994-18,544), 14,234 (12,045-17,474) and 18,441 (14,250-21,537) antibody phycoerythrin (PE) molecules bound/cell), and between infected and non-infected infants at 24 h (median (interquartile range): 17,772 (12,933-25,167) and 19,406 (14,885-24,225) antibody PE molecules bound/cell). The areas under the receiver operating characteristics (ROC) curves for HLA-DR, CD64 and CRP were 0.52-0.54, 0.88-0.94 and 0.75-0.77, respectively. We were unable to determine an optimal cutoff value for HLA-DR, as the diagnostic utilities of any cutoff point on the ROC curves were unable to satisfy the criteria (i.e. sensitivity and specificity >or=80%) for consideration as an useful diagnostic marker of infection. CONCLUSIONS: Our findings did not support the use of monocyte HLA-DR alone or in combination with other infection markers in the diagnosis of early-onset clinical infection and pneumonia in term newborns.

Biomarkers↗
PubMed1990

The diagnostic utility of desmin. A study of 584 cases and review of the literature.

The diagnostic utility of several antibodies against desmin and their optimal staining conditions have not been systematically evaluated. Sections of paraffin-embedded tissues from 584 cases were stained with a monoclonal antibody against desmin (Clone DER 11 from DAKO), using an avidin-biotin-peroxidase technique. The results were tabulated and compared with those from previous reports. The following observations were made: (1) When pronase digestion was performed before staining, desmin was equally demonstrable in tissues fixed in formalin, Zenker's, Bouin's, or B5 fixative; however, desmin staining was lost or significantly diminished in tissues fixed in absolute ethyl alcohol. In contrast, when pronase was not used, a positive staining was demonstrated only in tissue fixed in absolute ethyl alcohol. (2) Positive staining was found in normal muscle (92 of 92 cases), leiomyoma (12 of 13), rhabdomyoma (6 of 6), rhabdomyosarcoma (31 of 31), leiomyosarcoma (18 of 26). (3) Desmin was never found in epithelia, normal mesenchymal tissue other than muscle, tumors stimulating rhabdomyosarcoma, and epithelial tumors. (4) A positive staining was documented in 1 tumor (a fibrous histiocytoma) of 42 benign predominantly spindle cell tumors and in 8 of 89 predominantly spindle cell sarcomas. (5) Desmin was never documented in myoepithelial cells but stained myofibroblasts in 2 of 12 examples of granulation tissue and in 29 of 67 samples containing tumor-associated desmoplasia. The authors' data on the diagnostic sensitivity and specificity of the evaluated antibody should improve the use of desmin in diagnostic pathology.

Antibodies, Monoclonal↗
PubMed2005

Utilization management and noninvasive diagnostic imaging.

Health care costs are rising at unprecedented rates in the United States, and a substantial contributor to these cost increases is a growing dependence on diagnostic imaging. Radiologists have become aware of the need for optimal use of imaging provided in a cost-effective and timely manner. This article describes a program that has reduced inappropriate imaging use by involving both community-based and academic radiologists in its precertification process.

Cost Control↗