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PubMed1986

The diagnosis of multiple sclerosis. Contribution of non-clinical tests.

A group of 89 patients in whom multiple sclerosis (MS) has been clinically diagnosed with varying degrees of certainty, and 25 patients with optic neuritis (ON), were subjected to the following electrophysiological tests: visual evoked response (VER), auditory brainstem-evoked response (ABER), somatosensory-evoked response (SSER), blink reflex and electronystagmography (ENG). All these patients also underwent computerized tomography (CT scan) and analysis of cerebrospinal fluid (CSF). A new diagnostic procedure is proposed, combining optimum detection of definite MS with optimally economical use of the above-mentioned non-clinical tests. The results for the MS patients show that definite MS can be diagnosed much more frequently (72%) if abnormal results in the above-mentioned tests are accepted as evidence of a (subclinical) CNS lesion. Application of the clinical diagnostic criteria of McAlpine yielded "definite MS" only in 27% of our patient material. Our diagnostic criteria showed evidence for MS in 36% of the patients clinically diagnosed as having ON. The test results were inconclusive as regards the possibility of the remaining ON patients developing MS in the future.

Adult↗
PubMed1995

Optimization of prostate carcinoma staging: comparison of imaging and clinical methods.

PURPOSE: The diagnostic value of endorectal coil MRI, body coil MRI, transrectal ultrasound, digital rectal examination and PSA levels were prospectively analysed in order to define the most accurate preoperative staging method. METHODS: 33 patients with prostate carcinoma, who underwent subsequent prostatectomy, were enrolled in the study and examined on a 1.5T system using the body coil as well as the endorectal surface coil before and after the administration of contrast material. The results were compared to digital rectal examination, prostate specific antigen levels and endorectal ultrasound. RESULTS: Staging accuracy of endorectal coil MRI was 87.9% with a sensitivity of 88.9% and specificity of 86.7%. For body coil MRI, the staging accuracy was 75.7%, the sensitivity 66.7% and the specificity 87.9%, for transrectal ultrasound 69.6%, 41.7% and 100% and for the digital rectal examination 56.6%, 33.3% and 100%, respectively. Prediction was improved by combining results of endorectal coil MRI with PSA values. CONCLUSION: Endorectal ultrasound and digital rectal examination both had a tendency to underestimate the extent of the lesion. Endorectal coil MRI proved to be the best preoperative staging method. In combination with PSA values, diagnostic accuracy could be further improved. Therefore, local staging of prostate cancer could be based on these two parameters alone.

Aged↗
PubMed1979

Discrepancies between knowledge and use of diagnostic studies in asymptomatic patients.

The value of educational programs designed to promote optimal use of laboratory tests by physicians remains unsolved. To assess the effects of level of training and knowledge of test characteristics in determining laboratory ordering habits, physicians' use of laboratory tests as applied to asymptomatic patients was surveyed and their knowledge of four specific procedures was tested. The survey included 148 physicians both in training and in practice in Rochester, New York. Increased selectivity in the use of tests occurred during residency training, but selectivity correlated poorly with knowledge of test characteristics. These data underline the need for additional studies to determine the role of factors other than knowledge which contribute to the use of laboratory tests. Planners of cost containment programs and educational strategies will need to direct attention to these factors.

Clinical Laboratory Techniques↗
PubMed1996

Decision making with multiple goals: extending the threshold approach.

Given a set of conditions that may be present in a patient, this paper presents a methods for choosing the optimal combination of treatment actions, taking into account interactions among the available therapeutic and diagnostic procedures. The multiple-threshold approach is an extension of the threshold approach for individual conditions, and it offers a precise way of computing the optimal actions. In addition, tests for an example case show a 11-29% increase in the expected utility of treatments using this method.

Algorithms↗
PubMed1997

[Ways of optimizing the diagnosis and differential diagnosis of ocular tuberculosis].

The results of differential diagnostic study of 1035 patients with actual or suspected ocular tuberculosis in different aspects are analyzed. To define the diagnostic value of different signs, their comparative assessment was made via determination of the validity and informative value. Comparison of the findings with the efficiency of antituberculous therapy. In late posttherapeutical periods in particular was a reference for verification of the tuberculous etiology of eye diseases. There was strong evidence for the use of higher doses of tuberculin for diagnostic purposes due to its lower sensitivity. Focal tuberculin reactions were ascertained to be of no strict specificity and, if they were slightly pronounced, low informative value. The signs of the body's infection to tuberculin and of its sensitization were shown to suggest that the eye diseases might be of tuberculous etiology. A procedure for its verification was developed, based on the detection of specific ophthalmological picture, moderate or great focal tuberculin reactions by the type of inflammation and positive testing therapy with antituberculous agents. A programme (a system) of differentially diagnostic examination and an algorithm scheme aiding a physician to make a diagnosis and substantially reducing the frequency of misdiagnoses were proposed.

Adult↗
PubMed2004

Recent advances in light ion radiation therapy.

BACKGROUND: The fast development of energy- and intensity-modulated radiation therapy during the last two decades using photon and electron beams has when implemented resulted in a considerable improvement of radiation therapy, particularly if combined with radiobiologically based treatment optimization techniques. This has made intensity-modulated electron and photon beams as powerful as today's uniform dose proton therapy. To be able to cure also the most advanced hypoxic and radiation-resistant tumors of complex local spread, intensity-modulated light ion beams are really the ultimate tool and in clinical practice 2 to 3 times less expensive per patient treated than proton therapy. This development and the recent development of advanced tumor diagnostics based on PET-CT imaging of the tumor cell density open the field for new powerful radiobiologically based treatment optimization methods. The ultimate step is to use the unique radiobiologic and dose distributional advantages of light ion beams for truly optimized bioeffect planning where the integral three-dimensional dose delivery and tumor cell survival can be monitored by PET-CT imaging and corrected by biologically based adaptive therapy optimization methods. PURPOSE: The main purpose of the present paper is to discuss the principal areas of development of therapy optimization, by considering the therapy chain from tumor diagnostics and the use of three-dimensional predictive assay to biologically based treatment optimization with special focus on the rapid clinical development of advanced light ion therapy. METHODS: Besides the "classical" approaches using low ionization density hydrogen ions (protons, but also possibly deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be discussed. In the first one, lithium or beryllium or boron ions, which induce the least detrimental biologic effect to normal tissues for a given biologic effect in a small volume of the tumor, will be key particles. In the second approach, referred patients will be given a high-dose, high-precision "boost" treatment with carbon or oxygen ions during 1 week preceding the final treatment with conventional radiation in the referring hospital. The rationale behind these approaches is to minimize the high ionization density dose to the normal-tissue stroma outside but sometimes also inside the tumor bed and to ensure a more uniform and optimal biologic effectiveness in the tumor, also on the microscopic scale. The present discussion indicates that BIologically Optimized predictive Assay based light ion Radiation Therapy (Bio-Art) is really the ultimate way to perform high-precision radiation therapy using checkpoints of the integral dose delivery and the tumor response and, based on this information, perform compensating corrections of the dose delivery. By using biologically optimized scanned high-energy photon or ion beams, it is possible to measure in vivo the three-dimensional dose delivery using the same PET-CT camera that was used for diagnosing the tumor spread. This method thus opens up the door for truly three-dimensional biologically optimized adaptive radiation therapy, where the measured dose delivery to the true target tissues can be used to fine-adjust the incoming beams, so that possible errors in the integral therapy process are eliminated toward the end of the treatment. Interestingly enough, practically all major error sources--such as organ motion, treatment planning errors, patient setup errors, and dose delivery problems due to gantry, multileaf, or scanning beam errors--can be corrected for in this way. RESULTS AND CONCLUSIONS: Radiobiologically optimized dose delivery using intensity and radiation quality modulation based on high-resolution PET-CT or Magnetic Resonance Spectroscopic Imaging (MRSI)-based tumor and normal-tissue imaging is probably the ultimate development of radiation therapy, taking the unique physical and biologic advantages of light ions fully into account in truly patient-individualized curative treatment schedules. Using recently available biologically based treatment ilable biologically based treatment optimization algorithms, it is possible to improve the treatment outcome for advanced tumors by as much as 10-40%. The adaptive radiotherapy process based both on three-dimensional tumor cell survival and dose delivery monitoring has the potential of percent accuracy in tumor response and dose delivery monitoring, using two-dimensional, narrow high-energy photon beam scanning and three-dimensional (11)C Bragg peak scanning for radiation quality and intensity-modulated dose delivery. There is no doubt that the future of radiation therapy is very promising, and gradually more and more patients may not even need advanced surgery. Instead, they could be cured by biologically optimized electron, photon, or light ion therapy, where the densely ionizing Bragg peak is placed solely in the gross tumor, and a lower ionization density is used in microscopically invasive tumor volumes.

Cell Cycle↗
PubMed2005

Parenting stress and parental bonding.

Attachment experiences are thought to be important because of their implications for later development. The authors' aim with the questionnaire-based study was to investigate the differences between recalled parental bonding regarding 4 types of maternal and paternal bonding with respect to experienced parenting stress caused by child characteristics, parent attributes, and life events under the consideration of the child's gender and age. The authors gathered parental bonding behavior data with the German version of the Parental Bonding Instrument (PBI). The authors assessed parenting stress with their German version of the "Parenting Stress Index (PSI)." They found significant differences among 120 mothers grouped in the 4 maternal and the 4 paternal bonding types regarding parenting stress caused by child, maternal bonding: F(5, 113) = 4.13, p = .002, paternal bonding: F(5, 111) = 8.50, p < or = .0001, and parent characteristics, maternal bonding: F(5, 113) = 3.33, p = .008, paternal bonding: F(5, 111) = 7.80, p < or = .0001. The lowest level of parenting stress was experienced by mothers who themselves recalled the "optimal parental bonding type" with respect to the child and parental domain. The authors did not find any significant differences between the 4 maternal, F(5, 113) = 1.25, p = .29, and the 4 paternal, F(5, 111) = 1.87, p = .106, bonding types with respect to the life stress. According to the authors' findings, the representation of attachment relationships seems to have a special impact on the adult's capacity to cope with challenges and stress, either directly or indirectly as an internal working model of attachment. For the clinical practice, these findings seem to recommend the combination of both the PSI and PBI regarding the diagnostic of stressful mother-child system to plan an optimal intervention program.

Adult↗
PubMed1998

Bioanalytical calibration curves: proposal for statistical criteria.

Curve fitting procedures for bioanalytical assays are based on classical linear least squares (LSE) theory. A common procedure is to select among various models and weighting factors using the R2 as a goodness-of-fit criterion. It is questionable whether R2 is the most appropriate criterion for model selection. This is compounded by an often subjective removal of outliers. In this article, statistical curve fitting and diagnostic criteria are proposed. The fitting procedure is a Box-Cox-type power transformation of the data. The optimal transformation is obtained as the one that minimises the sum of squared deviations. Potential outlying standards are screened during the diagnostics stage as those whose jackknife percent deviations exceed 20%. The main advantage of this method is that it is objective and uniformly applicable across analytical techniques. Furthermore, the optimal transformation obtained in this way is unique. The results are demonstrated by comparing the power model to the R2 approach through the statistical analysis of 2094 analytical batches for 91 projects using various analytical techniques, namely GC, HPLC, LCMS and GCMS. The results indicate that the power model is robust and that QC batch acceptance using the power model is at least as good as the current method. These results hold true across all analytical techniques. It is thus strongly suggested that curve fitting and standard outlier detection for bioanalytical assays should be based on a power model and on jackknife percent deviations method with acceptable cut-off values.

Algorithms↗
PubMed1994

Normalization of spine densitometry.

We investigated several transformations of bone mineral content (BMC) and area density (BMD), in particular volumetric density (BMAD), to ascertain the influence on (1) body size dependence, (2) diagnostic sensitivity, and (3) precision. These transformations were examined in a group of 657 normal postmenopausal women and 327 women with osteoporotic fracture. First, expression of results as BMAD removed some of the slight dependence on body size; 21% of the variation in BMC and 15% of the variation i BMD were associated with body weight, but only 8% with BMAD. Second, the Z scores compared with those for age-matched controls for BMD and BMC were -1.85 and -1.71, respectively; the Z score for BMAD was -1.64. Third, the precision error for BMC was reduced by expressing results as BMD (1.1 versus 0.5%); BMAD degraded precision slightly (0.7%). BMD appeared to be the optimal expression for bone densitometry because it provided the best diagnostic sensitivity and lowest precision error; there was a minimal influence of body size on BMD results. This study also showed that osteoporotic women, even in the first postmenopausal decade, had low spine BMD, small vertebral area, and low body weight. Such women may be particularly at risk of crush fracture.

Absorptiometry, Photon↗
PubMed2006

Optimal labeling condition of antibodies available for immunofluorescence endoscopy.

PURPOSE: In recent years, labeled antibodies have been used for diagnostic imaging in many studies. In this study, we investigated the mode of binding in antibodies labeled with ICG derivatives newly developed for the diagnosis of microcarcinomas, and evaluated the optimal binding molar ratio between the labeling compounds and antibody. METHODS: MUC 1 antibody and ICG derivatives (ICG-ATT and ICG-sulfo-OSu) were used. ICG derivatives non-covalently bound to the antibody were removed with ethyl acetate, and the ratio of ICG derivatives covalently bound to the labeled antibody was confirmed. During purification of the labeled antibody, the amount of each labeling compound reacting with 1 molecule of the antibody varied as follows: 4, 8, 16, and 32 molar equivalents. Subsequently, the intensity of fluorescence was evaluated by spectroscopy and infrared fluoroscopy. RESULTS: The ratio of residual ICG derivative labeling the antibody was 67.4% for ICG-ATT and 65.0% for ICG-sulfo-OSu. When fluorescent antibody labeled with ICG-ATT at an F/P ratio of 2.94 or 4.18 was used, specific and clear fluorescent images of the antigen were obtained. When ICG-ATT-labeled antibody at an F/P ratio of 6.50 or 6.75 was used, the fluorescence intensity decreased and the fluorescent images of antigen became unclear. CONCLUSIONS: It was found that the ICG-ATT-labeled antibody was a more specific and sensitive marker than ICG-sulfo-OSu-labeled antibody, and that lower binding molar ratios of ICG-ATT were more useful for labeling the antibody.

Antibodies, Neoplasm↗
PubMed1997

Chronic hepatitis C.

BACKGROUND: Infection with the hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. Epidemiologic and natural history studies have helped to define the clinical impact of HCV infection, and molecular diagnostic assays have established clinical endpoints against which therapeutic regimens are currently tested. The absence of definitive therapy has generated controversy regarding indications and optimal candidacy for currently approved treatment. This paper reviews the epidemiology, natural history, clinical manifestations, diagnostic modalities, and current treatment of chronic HCV infection. METHODS: Search of the MEDLINE database for English-language articles and abstracts on chronic HCV infection yielded data from more than 500 original papers, reviews, and abstracts. RESULTS AND CONCLUSIONS: Hepatitis C virus is transmitted primarily through contaminated blood and less effectively by human body secretions, but a large proportion of patients have no clearly identifiable parenteral risk factors for viral acquisition. Infection with HCV results in subclinical chronic hepatitis in the majority of patients and may progress, usually over decades, to cirrhosis and hepatocellular carcinoma. Extrahepatic manifestations of HCV infection include porphyria cutanea tarda, mixed essential cryoglobulinemia, and membranoproliferative glomerulonephritis. Diagnostic modalities are accurate in estimating viral load and genotype and may be helpful in predicting and assessing response to treatment. Current therapy is limited to interferon alfa and is effective at viral eradication in only a small number of patients. The adjuvant use of drugs, such as ribavirin, in combination with interferon may hold promise at enhancing viral eradication. Understanding the mechanisms behind viral persistence and immune escape of HCV will be essential in developing effective future therapeutic and preventive strategies.

Antiviral Agents↗
PubMed2005

Solutions to the problem of bacterial resistance.

The recent increase in bacterial resistance has been, and continues to be, unmatched by drug discovery and development. The judicious use of antibacterials must be observed so as to contain bacterial resistance and maintain the utility of agents currently on the market. Appropriate antibacterial use involves antibacterial avoidance when not indicated. When indicated, appropriate antibacterial use dictates that the optimal drug, dose and duration be utilized. Professional society guidelines facilitate drug selection as well as outline diagnostic criteria and important considerations for patient stratification. Pharmacodynamics is also key for drug selection and often guides determination of not only the optimal drug but also the optimal dose and duration. Importantly, bacterial eradication is essential, as it will reduce clinical failure, recurrence, or relapse and prevent the selection of resistance. Additional strategies to influence antibacterial prescribing and use such as formal continuing medical education, printed educational materials, better diagnostic tests, and vaccination contribute to the efforts to minimize bacterial resistance and are also addressed.

Anti-Bacterial Agents↗
PubMed1984

Endoscopic training in the academic GI program. Program Directors Workshop, March 29 and 30, 1984, Atlanta, Georgia. How the GI pathologist can interact best with the GI trainee.

Effective collaboration between endoscopists is essential if optimal results from gastrointestinal biopsy are to be achieved. Agreed upon ways to enhance communication should be established, such as special requisition forms and regular conferences to discuss biopsy findings. Endoscopists and pathologists should know about and feel free to discuss the other specialist's procedures and techniques. Furthermore, all procedures and techniques for obtaining, handling, and reaching diagnostic conclusions from biopsy specimens need to be carefully examined and optimized. Recommended approaches are presented.

Biopsy↗
PubMed2001

The gamut of abdominal and pelvic cystic masses in children.

The gamut of abdominal and pelvic cystic masses in children is long with lesions affecting the urogenital tract and retroperitoneum, gastrointestinal tract and mesentery, hepatobiliary tract, and spleen. The goal of this pictorial review is to display the radiological manifestations of these disorders. The radiologist will learn, from this review of the differential diagnosis, how to reach a diagnosis after analyzing the characteristic findings using the appropriate imaging diagnostic studies among the various modalities available in his armamentarium, and the optimal management of these conditions.

Abdomen↗
PubMed2006

[Diagnostic imaging for connective tissue diseases].

Guidelines and diagnostic algorithms for the introduction of diagnostic procedures for connective tissue diseases have not yet been established and standardized. Diagnosis is often based on the patients's typical history, clinical symptoms and specific laboratory profiles. The use of diagnostic imaging procedures is relevant for differential diagnosis, for the assessment of disease activity and organ involvement, for defining the prognosis and monitoring responses to therapy and side effects. Experience with these techniques and diagnostic procedures, their application, indications and analysis represent the platform for rational and optimal diagnosis as well of defined therapy stratification.

Antiphospholipid Syndrome↗
PubMed2001

Diagnostic and prognostic significance of squamous cell carcinoma antigen in non-small cell lung cancer.

Squamous cell carcinoma antigen (SCC-Ag) is a glycoprotein secreted by non-small cell lung tumours (NSCLC). This study investigated the diagnostic and prognostic significance of SCC-Ag in NSCLC. Receiver operating characteristic (ROC) curve analysis was used to test the diagnostic performance of the SCC-Ag and determine the optimal threshold value in a group of 100 NSCLC patients undergoing surgery and 50 age matched healthy controls. This threshold was then prospectively validated in a group of 53 patients and 49 healthy controls. The prognostic significance of the preoperative SCC-Ag level and its postoperative decrease were tested using univariate and multivariate proportional hazard models. The area under the ROC curve was 0.71+/-0.04, and the best cutoff value was 1.4 ng/ml. This discriminated patients in the validation group, with a sensitivity of 0.55 and a specificity of 1.0. The hazard ratio was 0.144 (95% CI 0.074-0.281) for the postoperative decrease in the SCC Ag, and 5.823 (3.299-10.278) for the preoperative SCC Ag level. Multivariate analysis revealed that only disease stage and patients' age are strong prognostic factors for survival. In conclusion, the SCC-Ag serum level has moderate diagnostic role in NSCLC. Both the preoperative SCC-Ag level and its postoperative decrease have prognostic significance, yet inferior to the disease stage and the patient's age.

Adenocarcinoma↗
PubMedDate not supplied

[From farm to fork--Mycobacterium avium ssp. paratuberculosis (MAP) as zoonotic agent?].

Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of the paratuberculosis (Para Tb) in ruminants. In addition, this pathogen has been suspected to be implicated in the pathogenesis of Morbus Crohn disease (MC), causing chronic inflammatory intestine changes of humans. The participation of MAP in this illness is discussed intensively and has very contradictory opinions. On the one hand several times succeeded in proving MAP DNA in changed human tissues as well as, in recent time, the bacteria has been isolated from patient's blood. On the other hand there are many publications which support the opposite opinion. In critical evaluation of already available data, therefore the hypothesis can be formulated that MAP could possibly take part in the MC of humans. The reliable verification of this hypothesis will only be possible, if the diagnostic procedures can be refined upon the substantial deficit concerning the sensitivity and/or specificity of the diagnostic methods. In addition, till now there is lack of optimized statistically case control studies. The conceivable transmission of the bacteria to humans by the direct animal contact has been considered as possible vector, furthermore, MAP has been detected in pasteurised milk and other food of animal origin. The prevalence data, usually estimated by ELISA for milk cattle stock show over 80% prevalence in many counties of the Federal Republic of Germany with an individual case prevalence ranging between 1% and 17% in different stocks. Comparable data are present also from other countries as well as for small ruminants. MAP has been concerned as a global problem, moreover the high spreading rate of MAP in wild animal populations as well as the considerable ability of the bacteria to survive in different stages of the infectious- and contamination-cycle, which might hardly be broken through. Thus it requires intensive research efforts for the development of the methodical diagnostic process as basis for valid epidemiological investigations of animals, humans and food.

Animals↗
PubMed2003

MR imaging in abdominal emergencies.

The use of MR imaging in the emergency setting is evolving. Clear indications include situations in need of contrast media when iodinated contrast cannot be administered or to facilitate assessments in pregnant patients and children when exposure to ionizing radiation is considered unacceptable. The availability of rapid, motion-immune sequences now makes MR imaging a feasible study in less cooperative patients extending the range of patients for whom a diagnostic study can be achieved. Capitalizing on the unique benefits of MR imaging there is optimism that MR imaging can eliminate test redundancy and impact patient care in a cost-effective manner. Further investigations are needed to identify the diagnostic algorithms for which this favorable use holds true.

Abdomen, Acute↗