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Choosing optimal values of FEV1 and FEV1/FVC for surveillance for respiratory disorders in occupational populations.

Pulmonary lung-function testing plays an important role in surveillance programs for occupational respiratory disorders. Spirometry is usually utilized by applying preset cut-off values to discriminate between healthy and unhealthy subjects. This article demonstrates the usefulness of decision analysis techniques to arrive at an optimal diagnosis. The diagnostic performance of FEV1 and FEV1/FVC was evaluated by relative operating characteristics curves (ROCs) applied to data of a cohort gathered in 1965. Both parameters showed quite similar ROCs, with a maximal sensitivity of 40% at a specificity of 95% relative to the physician's diagnosis of respiratory disorder. The area under the curves was. 75 for both FEV1 and FEV1/FVC, illustrating that misclassification of 25% of the subjects is likely to occur. Regarding the consequences of a false-positive and a false-negative decision as of equal importance, the 5%-percentile (FEV1 residual less than -1.2 L) would be the optimal cut-off. An FEV1 residual below the lower 5%-percentile was six times more likely to appear in subjects with chronic nonspecific lung disease (CNSLD) than in subjects without. The post-test probability of CNSLD was three to four times the pre-test probability. In occupational or public health practice, however, false-positive results need to be avoided, even at the expense of a higher false-negative rate. In those situations, a more rigid cut-off between normal and abnormal values may be warranted.

Adult↗

Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene.

Straightforward detectable Duchenne muscular dystrophy (DMD) gene rearrangements, such as deletions or duplications involving an entire exon or more, are involved in about 70% of dystrophinopathies. In the remaining 30% a variety of point mutations or "small" mutations are suspected. Due to their diversity and to the large size and complexity of the DMD gene, these point mutations are difficult to detect. To overcome this diagnostic issue, we developed and optimized a routine muscle biopsy-based diagnostic strategy. The mutation detection rate is almost as high as 100% and mutations were identified in all patients for whom the diagnosis of DMD and Becker muscular dystrophy (BMD) was clinically suspected and further supported by the detection on Western blot of quantitative and/or qualitative dystrophin protein abnormalities. Here we report a total of 124 small mutations including 11 nonsense and frameshift mutations detected in BMD patients. In addition to a comprehensive assessment of muscular phenotypes that takes into account consequences of mutations on the expression of the dystrophin mRNA and protein, we provide and discuss genomic, mRNA, and protein data that pinpoint molecular mechanisms underlying BMD phenotypes associated with nonsense and frameshift mutations.

Adolescent↗

[Imaging of cartilage].

The motivation for cartilage repair is the preservation of adequate joint motion. Repairing joint surface congruity and providing balanced load bearing are crucial for this. MRI can contribute to this goal by describing number, depth, size, and distribution of cartilage lesions throughout the different joint compartments. Essential to such a contribution are adequate spatial resolution at a reasonable SNR together with good contrast between both cartilage and the subchondral bone as well as the joint space. For TSE sequences, this is achieved using TEs between 30 and 50 ms. Diagnostic accuracy is optimal when a lesion is depicted in more than one plane. Short TE, high bandwidth, and the appropriate orientation of the frequency encoding direction contribute to minimizing metal artifacts. Besides internal alterations of the cartilage's matrix, moderately T2-weighted TSE sequences sensitively depict bone marrow edema such as signal alterations and joint effusion, both contributing to highlight even subtle cartilage lesions. T1-weighted FS/WE 3D GE sequences profit from their high spatial resolution to appreciate gradual erosion of the cartilage. In OD the interface to the surrounding bone, the integrity of the overlying cartilage, and associated cysts are used to determine stability. The presence of two or more findings increases diagnostic accuracy. Prognosis is associated with the size of the affected area.

Cartilage↗

Thyroid nodule evaluation: what have we really learned from recent clinical guidelines?

Recent guidelines for the evaluation of thyroid nodules clarify the diagnostic algorithm while also reporting important differences. The performance of fine needle aspiration (FNA) for cytological examination follows serum TSH determination and thyroid ultrasonography. Thyroid scintigraphy is recommended following a low TSH value and/or FNA yielding an indeterminate follicular cytology. The use of thyroid ultrasonography is the source of some controversy: though it is recommended as a principal first test, its real-time use to guide FNA ranges from routine to only following an FNA yielding an inadequate or nondiagnostic cytological result. In clinical practice, the proportion of physicians utilizing ultrasonography, scintigraphy and FNA varies and frequently deviates from recommended guidelines. The development of guidelines is necessary to bring about consistency and optimization to the diagnostic work-up of thyroid nodules. It is likely that novel diagnostic procedures, such as molecular markers, large needle aspiration biopsy and thyroid imaging with tracers beyond conventional radioactive iodine or (99m)Tc pertechnetate, will lead to improved performance and implementation of guidelines.

Biopsy, Fine-Needle↗

Optimization of contrast agent volume for helical CT in the diagnostic assessment of patients with severe and multiple injuries.

PURPOSE: The aim of this study was to determine the optimal amount of contrast agent for helical CT of the trunk during primary radiologic evaluation of polytraumatized patients. METHOD: Eighty-three patients with severe and multiple injuries (mean age 36.2 years) underwent standardized helical CT examination with administration of a single contrast agent bolus of iohexol (Accupaque 300) at volumes of 120, 150, and 180 ml. Image quality was estimated by two blinded radiologists using a visual analogue scale. Analysis further included density measurements in regions of interest (ROIs) placed in the ascending, descending, and abdominal aorta as well as in the liver and spleen. RESULTS: The qualitative rating of the contrast agent effect after administration of 150 and 180 ml was significantly better compared with 120 ml [odds ratio (OR) 12.05, 95% confidence interval (CI) 3.50-41.52 and OR 12.14, 95% CI 3.36-43.85, respectively]. A dose increase from 120 to 150 ml resulted in a significantly better enhancement of the abdominal aorta (p = 0.006). The highest dose of 180 ml was not associated with a diagnostic gain in the other ROIs. CONCLUSION: We recommend administration of 150 ml of iohexol as the optimal amount of contrast material for single phase bolus administration in emergency helical CT examination of the chest and abdomen.

Abdominal Injuries↗

Information, discrimination and divergence in cytology. IV. Quality control in diagnostic cytology.

The performance of diagnostic cytology on Papanicolaou smears can be periodically monitored by calculating the total discrimination or the total divergence of the cytologic diagnoses against the histologic diagnoses on samples obtained by colposcope-directed biopsies. Using these measures, the annual performances of the Gynecologic Cytology Laboratory of the University of Minnesota between 1980 and 1988 were retrospectively analyzed. For those years, the total discrimination and total divergence behaved similarly and were sensitive to the performance of the total system, including specimen sampling errors and laboratory precision. The lowest limits of the permissible range of the total discrimination and total divergence were 0.15 and -1.21 decits, respectively, for a single-slide Papanicolaou test if an 80% "hit" rate was accepted as the lowest threshold for each category. The optimal numbers of category-states were not a sensitive indicator of the quality of a laboratory; i.e., the optimal number of diagnostic categories remained at three throughout the period studied.

Female↗

[Evaluation of informative value of laboratory tests and test complexes for the occupational diseases].

The authors discuss the criteria for rational selection of laboratory parameters most informative for the diagnosis of occupational diseases. Such criteria as diagnostic significance, diagnostic specificity, diagnostic informative value according to Kulback (Igx), and diagnostic selectiveness ensure the optimal selection of laboratory parameters for the diagnosis of occupational diseases. Diagnostic sensitivity is not a stable value, as it depends on the disease severity and degree of exposure to harmful factors. Basic requirements, which should be taken account of when selecting the complex of laboratory methods for the diagnosis of occupational diseases, are defined.

Clinical Laboratory Techniques↗

[Diagnostic imaging in liver cirrhosis].

For the diagnosis of liver cirrhosis ultrasound, computed tomography, magnetic resonance imaging, and angiography are recommended as imaging modalities. Ultrasound of the liver is used as a screening imaging tool in cases of patients suspicious for diffuse liver disease and is helpful in the term of follow-up examinations. Computed tomography is mainly performed to clarify the presence of liver disease detected by ultrasound. In this context, accurate examination of the vascular structures of the liver as well as extrahepatic situation, is of the essence. Diagnosis of diffuse liver disease and characterization of morphologic changes is improved using contrast-enhanced MR imaging with liver specific contrast media. Combined magnetic resonance imaging can provide comprehensive evaluation of cirrhosis. An improved detection rate and characterization of regenerating nodules can be achieved compared to imaging modalities such as ultrasound and computed tomography. MR imaging can be performed in a one-stop-technique using unenhanced and liver-specific-contrast-enhanced sequence protocols to evaluate the liver parenchyma itself, MR cholangiography to verify the bile duct system, and MR angiography to specify the vascular situation. This technique is the optimal protocol for diagnostic imaging in patients suffering from liver cirrhosis and the method of choice to reach the final diagnosis.

Diagnostic Imaging↗

Comparative sensitivity and specificity of exercise electrocardiographic lead systems.

A comparison of current exercise electrocardiographic lead systems reveals differences in the sensitivity and specificity of S-T segment shifts diagnostic of obstructive coronary artery disease. The differences are explained in part by differences in population samples, lead systems and criteria for positivity. Multiple electrocardiographic lead recording in symptomatic patients during and after exercise improves sensitivity in detecting S-T segment shifts with only a small decrease in specificity. A review of population screening studies in asymptomatic subjects shows a wide selection of different exercise electrocardiographic lead systems and criteria for a positive test. Few screening studies have compared the prevalence of different S-T segment configurations in individual leads of a simultaneously recorded multiple lead system during or after exercise. Data from animal studies of myocardial ischemia suggest why 100 percent sensitivity in detecting obstructive coronary disease is unlikely to be obtained with surface electrocardiographic recordings. Additional research is required to identify the optimal set of diagnostic exercise electrocardiographic leads and criteria for positivity so that maximal predictive accuracy can be obtained for different patient subsets.

Adolescent↗

[Diagnosis of common bile duct stones in symptomatic gallstone disease].

It is unclear which diagnostic procedure is optimal for the detection of common bile duct stones prior to laparoscopic cholecystectomy. It is routine to use blood tests for liver function and transabdominal ultrasound, and the best method is currently to continue evaluation with other methods when one or more blood tests for liver function are elevated and/or the diameter of the common bile duct is > or = 10 mm on transabdominal ultrasound. Magnetic resonance cholangiography, endoscopic ultrasound, laparoscopic ultrasound, intraoperative cholangiography and endoscopic retrograde cholangiography are all accurate in the detection of common bile duct stones. Intravenous cholangiography and computer tomography needs further evaluation before final recommendations can be made. Intraoperative cholangiography and endoscopic retrograde cholangiography have the best documentation available in the literature. Intraoperative cholangiography is easy, cheap and without significant complications, whereas endoscopic retrograde cholangiography has a high morbidity and mortality rate. Endoscopic retrograde cholangiography is therefore not suitable as a diagnostic test and should be abandoned as such in the future. Patients with cholangitis, jaundice and common bile duct stones visualised by transabdominal ultrasound have a high risk of common bile duct stones, and these patients can therefore undergo endoscopic retrograde cholangiography directly. Other patients should have a magnetic resonance cholangiography or endoscopic ultrasound preoperatively, or intraoperative cholangiography or laparoscopic ultrasound depending on local factors such as available equipment and surgical expertise.

Cholangiography↗

Relationship between perioperative troponin elevation and other indicators of myocardial injury in vascular surgery patients.

BACKGROUND: In 2000 the European Society of Cardiology and the American College of Cardiology published a consensus document revising the definition of myocardial infarction. The usefulness of this revised definition has been challenged. It has been suggested that, rather than any release of cardiac troponin being potentially diagnostic of myocardial infarction, a diagnostic threshold consistent with significant myocardial injury should be defined. METHODS: We studied 65 patients undergoing elective major vascular surgery to examine the relationship between the magnitude of cardiac troponin I (cTnI) and creatine kinase MB fraction (CK-MB) release and clinical signs or symptoms of myocardial injury. cTnI and CK-MB concentrations were measured preoperatively and on the first 4 postoperative days using the ACCESS assay (Beckmann). Patients were considered to have suffered a perioperative myocardial infarction if they had either symptoms or ECG changes consistent with this diagnosis, together with cTnI release. RESULTS: Peak postoperative cTnI concentrations above the lower detection limit of the ACCESS assay (0.06 microg litre(-1)) occurred in 26 patients. Eight of these patients displayed symptoms or ECG changes consistent with myocardial injury. A cTnI level greater than 0.68 microg litre(-1) was found to be consistent with the clinical diagnosis of myocardial infarction. The optimal cut-off for the diagnosis of MI using CK-MB was 40.4 microg litre(-1). CONCLUSIONS: These data suggest that further studies are required to define the optimal cardiac troponin diagnostic threshold for the diagnosis of myocardial infarction in the non-cardiac surgery population.

Aged↗

Diagnostic value of Tl-201 lung uptake is dependent on measurement method.

BACKGROUND: Increased lung uptake during exercise thallium 201 single photon emission computed tomography is related to left ventricular dysfunction and extent of coronary artery disease (CAD). We studied the influence of the lung region of interest (ROI), used to quantify Tl-201 lung uptake, on the diagnostic value of the lung-to-heart uptake ratio (LHR) in detecting CAD with Tl-201 myocardial single photon emission computed tomography. METHODS AND RESULTS: We retrospectively studied 152 consecutive patients referred to our center for stress Tl-201 scanning. Of these, 116 had proven multivessel CAD and 36 had either normal findings on coronary angiogram or a low likelihood (<5%) of CAD. Poststress quantitative analysis was performed from a 4 x 4-pixel ROI over the hottest myocardial region, an 8 x 8-pixel left lung ROI, an 8 x 8-pixel right lung ROI, and a manual ROI encompassing the whole right lung. The LHR was calculated for each lung ROI. Right LHR (R-LHR) provided the best interobserver and intraobserver reproducibility. R-LHR and total R-LHR values were significantly higher in patients with CAD. Only history of myocardial infarction significantly influenced the R-LHR measurement. CONCLUSIONS: The methodology of LHR measurement significantly influences the clinical contribution of Tl-201 lung uptake evaluation. Optimal reproducibility and diagnostic accuracy are provided by a right lung ROI.

Aged↗

Safety and ultrasound-enhancing potentials of a new sulfur hexafluoride-containing agent in the cerebral circulation.

Insufficient ultrasound penetration through the temporal bone is a serious limitation of transcranial ultrasound diagnostics. In a phase I study, the authors studied safety and ultrasound enhancing potentials of the new transpulmonary ultrasound contrast agent SonoVue, which contains sulfur hexafluoride gas microbubbles stabilized by a phospholipid shell. Twelve healthy volunteers received four different doses of SonoVue (0.3 ml, 0.6 ml, 1.2 ml, and 2.4 ml) intravenously. The duration of ultrasound contrast enhancement was measured by transcranial Doppler sonography (TCD) and transcranial color-coded sonography (TCCS). Safety and tolerability was monitored during the study and for 24 hours after contrast agent administration. TCD: Duration of spectral enhancement (signal intensity of 5 dB over baseline) was observed dose-related (p < 0.0001; Friedman-test) for (0.3 ml) 136 +/- 63.4 seconds; (0.6 ml) 191 +/- 63.3 seconds; (1.2 ml) 314 +/- 88 seconds; (2.4 ml) 434 +/- 168 seconds [mean +/- SD]. Dependent on dosage, the peak signal amplification in TCD was significantly different (p < 0.001; Friedman-test) as well: (0.3 ml) 24.5 +/- 2.0 dB; (0.6 ml) 26.0 +/- 1.6 dB; (1.2 ml) 27.6 +/- 2.2 dB; (2.4 ml) 28.4 +/- 2.2 dB (mean +/- SD). TCCS: Mean time of optimal enhancement increased from 214 +/- 73 seconds (0.3 ml) to 356 +/- 14 seconds (2.4 ml) in a dose-dependent manner. In TCCS, signal amplification appeared to be stronger with increasing doses. Adverse events were not observed during the study. This investigation describes the ultrasound enhancing potential of SonoVue in the intracranial cerebral circulation. SonoVue proved to be well tolerated and provided a long-lasting ultrasound contrast enhancement that supports an optimal transcranial ultrasound diagnostic.

Adult↗

Operation of an allergen-extract pharmacy.

The quality control (QC) and quality assurance (QA) systems for a military allergen-extract pharmacy are described. The United States Army Allergen Extract Laboratory (USAAEL) provides diagnostic and therapeutic allergen-extract materials to military personnel throughout the world. More than 40,000 individualized prescriptions are compounded annually. The staff is composed of one pharmacist, 16 medical technicians, and four clerical, two inventory, and three supervisory personnel. Each prescription takes about one man-hour to prepare. The technicians are trained in aseptic technique, allergen-extract compounding, and the diagnosis and treatment of allergies during an eight-week program. Following a physician-allergist's evaluation of a patient, a prescription is written with a formula itemizing the specific allergen components, their relative concentrations, and a treatment schedule. Patient profile cards are kept on every patient. A complete record of patient, prescriber, demographic data, allergen formula, treatment schedule, lots, and initials of personnel responsible at each step allow a thorough assessment for QC and QA. The identity and volume of each allergen in every prescription are checked twice. A multitiered QC system is used to identify problems and errors. A QA and QC assessment was conducted on more than 18,000 prescriptions received during a six-month period. More than 99% of all known errors were discovered before the prescriptions were dispensed. Allergen-extract prescriptions must be accurate, precise, and reproducible to be effective and to avoid adverse reactions. Pharmacists can play a vital role in ensuring the optimal quality of diagnostic and therapeutic allergen extracts.

Allergens↗

The diagnostic use of the rhTSH/thyroglobulin test in differentiated thyroid cancer patients with persistent disease and low thyroglobulin levels.

BACKGROUND: Serum thyroglobulin (Tg) measurement after TSH stimulation, by either thyroid hormone withdrawal or recombinant human TSH (rhTSH) administration, is the most sensitive method for early detection of patients with persistent or recurrent differentiated thyroid cancer (DTC) after total thyroidectomy and 131I ablation. The use of rhTSH is now increasing because it avoids thyroid hormone suppressive therapy (THST) withdrawal and the consequent symptoms of severe hypothyroidism. Current guidelines suggest measurement of serum Tg 4 days after starting a 2-day course of rhTSH injections, and assumes that Tg reaches maximum serum levels at that time. OBJECTIVE: The present study was carried out to evaluate the accuracy of rhTSH/thyroglobulin test in DTC patients with persistent disease and low thyroglobulin levels. PATIENTS AND MEASUREMENTS: A series of 13 DTC patients was selected because they had proven persistent disease associated with low Tg levels (< 2.0 micro g/l) under l-thyroxine treatment. In all of them, serum Tg was > 5.0 micro g/l at the last THST withdrawal. We measured serum Tg and TSH levels on days 0.5, 1, 1.5, 2, 4, 7, 10 and 15 after the first of a 2-day course of intramuscular rhTSH injections. RESULTS: Serum Tg values were variable in terms of both peak and time-course. Detectable serum Tg levels were recorded on day 4 in all patients. However, among these 13 patients, the peak Tg value was reached earlier than day 4 in three patients and later in two others. In one patient, Tg level at day 2 was higher (3.0 micro g/l) than at day 4 (1.8 micro g/l). In six of the 13 patients studied we compared Tg values after rhTSH to those subsequently obtained after THST withdrawal: in five of them Tg values were two to three times higher after the latter stimulation. Serum Tg value variability after rhTSH was partially accounted for by variability of serum TSH levels, which were inversely related to patient body surface. CONCLUSIONS: In DTC patients with persistent disease and low Tg levels, optimization of the diagnostic use of Tg measurement after rhTSH may require rhTSH dose adjustment to the patient body surface area and repeated blood sampling, in order to improve diagnostic accuracy. In these patients not even a TSH-stimulated serum Tg cut-off of 2.0 micro g/l on day 4 provides 100% accuracy, whereas a cut-off of 1.0 micro g/l seems more appropriate. Therefore, in this subset of patients, if any detectable Tg level >or= 1.0 micro g/l is found after rhTSH, re-evaluation after THST should be advised.

Adult↗

Estimation of the noisy component of anatomical backgrounds.

The knowledge of the relationship that links radiation dose and image quality is a prerequisite to any optimization of medical diagnostic radiology. Image quality depends, on the one hand, on the physical parameters such as contrast, resolution, and noise, and on the other hand, on characteristics of the observer that assesses the image. While the role of contrast and resolution is precisely defined and recognized, the influence of image noise is not yet fully understood. Its measurement is often based on imaging uniform test objects, even though real images contain anatomical backgrounds whose statistical nature is much different from test objects used to assess system noise. The goal of this study was to demonstrate the importance of variations in background anatomy by quantifying its effect on a series of detection tasks. Several types of mammographic backgrounds and signals were examined by psychophysical experiments in a two-alternative forced-choice detection task. According to hypotheses concerning the strategy used by the human observers, their signal to noise ratio was determined. This variable was also computed for a mathematical model based on the statistical decision theory. By comparing theoretical model and experimental results, the way that anatomical structure is perceived has been analyzed. Experiments showed that the observer's behavior was highly dependent upon both system noise and the anatomical background. The anatomy partly acts as a signal recognizable as such and partly as a pure noise that disturbs the detection process. This dual nature of the anatomy is quantified. It is shown that its effect varies according to its amplitude and the profile of the object being detected. The importance of the noisy part of the anatomy is, in some situations, much greater than the system noise. Hence, reducing the system noise by increasing the dose will not improve task performance. This observation indicates that the tradeoff between dose and image quality might be optimized by accepting a higher system noise. This could lead to a better resolution, more contrast, or less dose.

Biophysics↗

Simultaneous use of a diagnostic catheter to facilitate stent deployment in aorto-ostial artery stenosis: a case report.

Correct positioning of a stent at an ostial lesion can be difficult due to poor visualisation once the guide is backed out of the artery to allow deployment. This case report illustrates a technique whereby the simultaneous use of a diagnostic catheter allows optimal visualisation of stent position, whilst maintaining a stable guide position well away from the stent.

Aged↗

Concurrent validity of the GMS-AGECAT (A3) package in a Danish nursing home population.

AIM: To validate the Danish version of the GMS-AGECAT (A3), the Standardized Mini Mental State Examination (SMMSE) and the Geriatric Depression Scale-15 (GDS-15) by comparing them to clinical ICD-10 criteria in a Danish nursing home population. METHODS: With a participation of 91%, the study included 100 residents. All residents were interviewed with the GMS-AGECAT (A3), SMMSE and GDS-15 by an MD and then blindly diagnosed by a consultant geriatric psychiatrist. All residents approached for an interview were included, also those who were not able to communicate (the non-accessibles). RESULTS: The prevalence of clinical psychiatric ICD-10 main diagnoses was 56%. The non-accessibles had significantly higher psychiatric morbidity and lower ADL scores (modified Barthel ADL index) compared to those who were able to communicate. With the non-accessibles (N = 100) included, the optimal screening and diagnostic cutpoint for the GMS-AGECAT organic diagnoses was 2/3, with 96% sensitivity, 73% specificity, 77% predictive value of a positive test and 95% predictive value of a negative test. The SMMSE and GDS-15 had better screening properties compared to the GMS-AGECAT but only 60% of the residents were able to complete the SMMSE and 78% were able to complete the GDS-15. CONCLUSION: The Danish version of the GMS-AGECAT has relevant diagnostic and screening properties for organic disorders in Danish nursing home populations.

Aged↗