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[Influence of positron emission tomography on surgical therapy planning in recurrent colorectal cancer].

The advantages of PET are high sensitivity and specificity for the detection of local tumor relapse, especially in comparison with conventional imaging techniques. Furthermore, there is an additional value of FDG-PET for the detection of tumor manifestations associated with a tumor marker (e.g. serum CEA) increase without suspicious findings in other diagnostic procedures. The methodological advantage of a whole-body examination further improves the detectability of distant metastases. Thus, FDG-PET may induce a change in the therapeutic concept in recurrent colorectal cancer in approximately 30% of cases, concerning the indication for surgery as well as the use of multimodal surgical concepts. By means of the metabolic functional approach FDG-PET offers the possibility of therapy monitoring. This enables very early and more specific indication of response to preoperative therapies or of the presence of residual disease after surgical tumor resection or interventional tumor ablation of metastases or recurrences. PET using new tracer molecules demonstrates an additional advantage of the technique regarding the determination of the micromilieu of a tumor (vascularity, proliferation) compared with all other non-invasive diagnostic methods. This opens up new possibilities to optimize surgical therapy planning and prognostic evaluation.

Adult↗

Squamous cell carcinoma of the larynx in HIV-positive patients: difficulties in diagnosis and management.

Patients who are infected with human immunodeficiency virus (HIV) are at increased risk of developing laryngeal squamous cell carcinoma. This malignancy on average appears in a younger age group at a more advanced stage and has a more aggressive course in HIV patients. These patients have difficult management challenges, diagnostically, in staging, and particularly in determining the optimal treatment for each individual patient because their underlying HIV infection can markedly increase morbidity associated with active treatments. They frequently have problems associated with swallowing both before and after treatment. We present two cases that highlight difficulties in the diagnosis and management of these patients as well as post-treatment complications, with particular emphasis on swallowing problems.

Adult↗

Clinical proteomics: from biomarker discovery and cell signaling profiles to individualized personal therapy.

The discovery of new highly sensitive and specific biomarkers for early disease detection and risk stratification coupled with the development of personalized "designer" therapies holds the key to future treatment of complex diseases such as cancer. Mounting evidence confirms that the low molecular weight (LMW) range of the circulatory proteome contains a rich source of information that may be able to detect early stage disease and stratify risk. Current mass spectrometry (MS) platforms can generate a rapid and high resolution portrait of the LMW proteome. Emerging novel nanotechnology strategies to amplify and harvest these LMW biomarkers in vivo or ex vivo will greatly enhance our ability to discover and characterize molecules for early disease detection, subclassification and prognostic capability of current proteomics modalities. Ultimately genetic mutations giving rise to disease are played out and manifested on a protein level, involving derangements in protein function and information flow within diseased cells and the interconnected tissue microenvironment. Newly developed highly sensitive, specific and linearly dynamic reverse phase protein microarray systems are now able to generate circuit maps of information flow through phosphoprotein networks of pure populations of microdissected tumor cells obtained from patient biopsies. We postulate that this type of enabling technology will provide the foundation for the development of individualized combinatorial therapies of molecular inhibitors to target tumor-specific deranged pathways regulating key biologic processes including proliferation, differentiation, apoptosis, immunity and metastasis. Hence future therapies will be tailored to the specific deranged molecular circuitry of an individual patient's disease. The successful transition of these groundbreaking proteomic technologies from research tools to integrated clinical diagnostic platforms will require ongoing continued development, and optimization with rigorous standardization development and quality control procedures.

Biomarkers↗

Amebiasis: Clinical Implications of the Recognition of Entamoeba dispar.

Entamoeba histolytica was recently reclassified to recognize the existence of two genetically distinct but morphologically indistinguishable species: E. histolytica, the protozoan parasite that causes amebic dysentery and liver abscess, and Entamoeba dispar, a nonpathogenic intestinal parasite. Acceptance of this redefinition has dramatically changed both our understanding of the true epidemiology of E. histolytica and the optimal methods for diagnosing amebiasis. Molecular-based diagnostic tests using polymerase chain reaction (PCR) to amplify amebic DNA or enzyme-linked immunosorbent assay (ELISA) to identify amebic antigens in stool samples have been developed to distinguish infection with E. histolytica from infection with E. dispar. Because of its ability to differentiate strains of E. histolytica, PCR is a very useful research tool. Only the ELISA-based test is simple to perform, making it clinically useful in the developing world. To avoid unnecessary treatment of individuals infected with E. dispar, the World Health Organization has stressed the importance of making a specific diagnosis of E. histolytica infection (not E. histolytica/E. dispar) before treating for amebiasis.

Journal Article↗

Cardiac surgery for adults with mental retardation. Dilemmas in management.

In summary, cardiac surgery for adults with mental retardation raises a series of controversial legal, economic, ethical, medical, and nursing dilemmas. During the past 20 years, many improvements have taken place in the care of these patients. However, in the future, judicial and statutory mandates requiring high-quality medical care for persons with mental retardation may conflict increasingly with hospital cost-control legislation and thereby affect clinical decisions. For example, it is conceivable that elective repair of an ostium secundum atrial septal defect in an asymptomatic patient will expend the limited resources necessary to carry out emergency revascularization in a symptomatic patient with impending myocardial infarction. This issue becomes even more delicate when the asymptomatic patient is a mentally retarded ward of the state, and the symptomatic patient is a middle-aged man supporting a wife and several college-age children. There may be no easy solution to this problem, and it will provide the grist for many bioethicists. Fortunately, from a practical point of view, we do not currently have to choose between these patients to receive treatment. Our hope is that health care for mentally retarded patients will not be compromised. We believe that decisions about patient management should be based on enlightened clinical judgment rather than on preconceived notions about this population. In the quest for optimal health care delivery, the special needs of these patients should be considered when cardiac catheterization and possible cardiac surgery are contemplated. Although we have presented an approach to a patient with cardiac disease requiring cardiac surgery, we believe that this approach can be utilized for any retarded patient requiring acute medical care. Currently, because there has not been much training in this area, many physicians and nurses lack first-hand experience in caring for the mentally retarded. This inexperience may lead to difficulty in making appropriate decisions. Therefore, we advocate additional exposure in medical and nursing school curricula to the complex health care needs of this population. In conclusion, there appear to be two major issues that pose dilemmas: first, acceptance of the rights of this population to optimal medical management and, second, implementation of appropriate diagnostic and therapeutic strategies.

Adult↗

Alzheimer's disease.

Alzheimer's disease is a complex and fascinating entity, clinically and neurobiologically. Although originally described as a form of accelerated aging in an article that emphasized neuropathology, it is now considered a specific age-related disease entity, at whatever age it occurs. It is the most common cause of the dementia syndrome, probably the fourth most common cause of death in the United States and is likely to become more common as the population ages. The course is typically an insidious onset of cognitive and behavioral impairment progressing more or less steadily over years to profound disability. The classic pathologic changes are Alzheimer plaques, neurofibrillary tangles, and loss of subcortical cells, including particularly the cholinergic cells of the nucleus basalis complex. The functional disability can be correlated with the site and extent of brain damage, but why these cells deteriorate and die is not known. Diagnosis depends on identifying the dementia syndrome in a patient whose course is compatible with Alzheimer's disease and in whom no other factors adequate to explain the dementia are found. NIH consensus diagnostic criteria are now available. Care is symptomatic optimal care of intercurrent illness, and pharmacologic, behavioral, and social "splints" to maximize the function of the remaining brain. Specific treatments are still in the realm of research, and both clinical and basic research on this challenging disorder are active and accelerating.

Aged↗

A novel method of microwave treatment for detection of cytoplasmic and nuclear antigens by flow cytometry.

Flow cytometry has recently become a useful technique for the quantitative analysis of cytoplasmic and nuclear antigens. We report here a rapid, simple, reproducible, and sensitive method for the simultaneous detection of cytoplasmic and nuclear antigens by flow cytometry. This technique involves the treatment of cell suspensions with 60 s of microwave oven heating after fixation with 2% paraformaldehyde. Following this treatment a number of cytoplasmic and nuclear antigens were detected on the human myelomonocytic cell line U937 (CD68, PCNA and Ki-67), peripheral blood leukocytes from both normal donors and leukemia patients (CD68, lipocortin-1 and PCNA) and a rat mesangial cell line 1097 (desmin, alpha-smooth muscle actin) using a standard indirect immunofluorescent staining with mouse monoclonal antibodies (mAbs). There are several advantages of this technique over the routinely used methods currently available. Firstly, microwave treatment is a rapid, simple, and reproducible method, which largely reduces both time and cost expenditure, and makes this technique widely available for flow cytometric analysis in many areas of diagnostic and research purposes. Secondly, microwave treatment produces optimal results for simultaneous detection of both cytoplasmic (CD68, lipocortin-1, desmin, alpha-smooth actin) and nuclear (PCNA, Ki67) antigens. Thirdly, microwave treatment also produces a discrete profile for DNA content analysis. Finally, microwaving retains a clear discrimination between cells and debris as measured by light scatter. This study demonstrates that microwave treatment is a powerful technique which will be particularly applicable to flow cytometric analysis in the detection of many cytoplasmic and nuclear antigens.

Animals↗

Three dimensional ultrasound: display modalities in the fetal spine and thorax.

PURPOSE: To evaluate the display modalities of three dimensional ultrasound (3D US) in the prenatal assessment of the fetal spine and thorax. METHOD: Twenty prenatal spine examinations (mean gestational age: 21 weeks, 15 normal findings, five pathological cases) were performed with a commercially available 3D US device. The visualization of fetal spine and rib anatomy and pathology by 3D US display was evaluated using various rendering methods and the optimal method was determined in regard to comprehensive diagnostic display. RESULTS: Demonstration of continuity of both the spine and the ribs could be achieved by 3D US. Visualization of clavicles, scapula and iliac bone was possible on rendered images. CONCLUSION: 3D US offers an additional diagnostic tool for prenatal assessment of the fetal spine and ribs; it provides a continuous demonstration of curved or tortuous structures in the rendered image. It improves comprehension of complex anatomy by providing a simultaneous display of all orthogonal sectional planes.

Female↗

Labeling and comparative biodistribution of the monoclonal antibody KS1/4 in nude mice bearing human lung adenocarcinoma.

In order to evaluate some of the key factors that may allow the optimization of radiolabeled monoclonal antibodies for use as diagnostic and therapeutic tools to detect and treat human neoplasia, we compared the biodistribution of the anti-lung-tumor monoclonal antibody KS1/4, labeled with four different radionuclides, in athymic (nu/nu) mice bearing human lung adenocarcinoma. Several radiolabeling methods were used: the first involved coupling a suitable bifunctional chelating agent, such as DTPA, to the KS1/4 monoclonal antibody, followed by binding the radiometal, either 113mIn or 111In. Radioiodination was carried out by the chloramine-T method with 131I, and intrinsic labeling by generating the hybridoma in the presence of 75Se-methionine. An examination of tumors and major organs of mice injected with one of the above radiolabeled KS1/4 MoAbs, and biodistribution at various time intervals up to 96 h post injection revealed that iodination and intrinsic labeling yield the highest tumor uptake. Because of the relatively high deiodination that occurs in vivo, and the high 75Se content in the circulation, the preferential uptake (tumor-to-blood ratio) of these radiopharmaceuticals lags behind the equivalent ratios for the In-labeled MoAb. In the latter group of animals, a second consecutive injection of the labeled MoAb resulted in elevated blood level of radioindium, as well as a corresponding decrease in tumor-to-blood ratios.

Adenocarcinoma↗

Immunoscintigraphy of bone sarcomas--results in 5 patients.

The feasibility of using the murine monoclonal antibody, TP-1, for clinical immunoscintigraphy was examined in a pilot study involving 5 patients with bone sarcomas. 131I-labelled F(ab')2 antibody fragments were injected in doses of 0.8-1.0 mg (90-130 MBq), and the accumulation of radioactivity was examined by scintigraphy, and assessed by direct measurements on biopsied tumour and normal tissue. One osteosarcoma patient had a primary tumour in the femur, whereas the other 4 had single lung metastases detected by other diagnostic methods. Immunoscintigraphy of the femoral primary was optimally visualised after 22 h. In 2 patients, the method failed to detect lung metastasis, in 1 of the cases possibly related to less than optimal methodological conditions. In 2 other patients, increased accumulation of radioactivity indicated one and three lung tumours, in addition to the single metastasis observed by X-ray and CT scanning, tumours that were later confirmed and removed surgically. The concentration of radioactivity in tumour and normal tissues 44-72 h after antibody injection could be measured in 4 patients. The tumour to blood ratios were in the range of 1.2-4.2, compared to 0.1-0.8 for various normal tissues. The results indicate that immunoscintigraphy with TP-1 antibody fragments have a potential for early detection of lung metastases in patients with bone sarcoma.

Adolescent↗

Additional diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis.

In the past decade significant advantages have been made in the treatment of rheumatoid arthritis (RA) and therapeutic strategies have changed a lot. These days, highly effective disease modifying anti-rheumatic drugs enable intervention early in the disease process, in order to prevent major joint damage. For years, serological support in the diagnosis of RA has been limited to the presence of rheumatoid factors, although not very specific for RA. During the last years a variety of circulating non-RF antibodies have been discovered and reported to be of potential diagnostic value. CCP2 proved to be a very disease-specific and even sensitive marker for RA. In addition to the diagnostic properties, CCP showed to be a good prognostic marker, CCP helps to predict the erosive or nonerosive progression of the disease, and CCP is already present early in the disease. This diagnostic tool enables the clinician to choose the optimal therapeutic management for each single RA patient.

Antibodies↗

Management of infections in critically ill neutropenic cancer patients.

Because of improving antineoplastic treatment options with increasing cure rates, prolonging survival, and improving quality of life, the reluctance to admit patients with malignant disease to an intensive care unit is not justified; thus, the number of patients with malignancies treated in intensive care units rises. The use of more aggressive anticancer regimens leads to an increase of attendant infections, which are the most frequent and often life-threatening complications in cancer patients. A multidisciplinary practical approach to evaluation and treatment is needed to optimize treatment results and to meet the various diagnostic and therapeutic challenges in this subset of patients on an intensive care unit.

Anti-Infective Agents↗

Head and neck imaging at 3T.

For the theoretic advantages of 3T units to translate to improved diagnostic quality, careful attention must be paid to optimization of pulse sequences and development of clinically feasible imaging protocols. RARE sequences continue to be the choice for routine clinical imaging of the head and neck; although exquisite T2W images are afforded, T1W imaging is problematic. Short ETLT1W RARE imaging seems to be a good compromise.

Artifacts↗

Capillary glucose determination in the screening of gestational diabetes.

Paired capillary-venous blood samples were obtained from 418 pregnant women undergoing an oral glucose challenge test (GCT) for the screening of gestational diabetes (GD). The relationship between capillary and plasma glucose concentrations was investigated in order to establish a capillary GCT threshold. Plasma glucose was assayed by the glucose oxidase method and capillary glucose using Reflocheck Glucose strips and a Reflocheck reflectance meter. During GCT the capillary values exceeded plasma glucose values by a mean difference of 10-12 mg/dl fasting and 22-24 mg/dl after 1 h. A high correlation between the glucose values of the two techniques was found, particularly for those at 1 h, with corresponding capillary determinations being 20 mg/dl above plasma values. The sensitivity, specificity and predictive value of the various capillary thresholds investigated in detecting GD corresponded substantially to the accuracy of plasma thresholds 20 mg/dl lower. The receiver operator characteristic curves of the plasma and capillary thresholds were similar in shape and the optimal cut-off point for performing a diagnostic test was set at 135 and 155 mg/dl, respectively. These cut-off values should be reconsidered in the light of the costs and perinatal outcome.

Adult↗

MR imaging of the liver: techniques and clinical applications.

With a recent advance of fast MR imaging techniques including fast gradient-echo (GRE), fast spin-echo (FSE), single shot FSE (SSFSE) and echo-planar imaging (EPI), and availability of a phased-array torso coil, there can be many possible pulse sequences for liver MR imaging. In clinical practice, optimization of pulse sequences is important for improving diagnostic performance of liver diseases. In this article, we review the current status of liver MR imaging, focusing on the description of standard pulse sequences, and the utility of fast scanning technique and contrast-enhancement studies.

Carcinoma, Hepatocellular↗

Impact of radionuclide techniques on evaluation of patients with ischemic heart disease.

Radiotracer studies of the heart have become clinically important in the last decade, especially for evaluation of patients with known or suspected ischemic heart disease. Radionuclide ventriculography provides quantitative measures of biventricular function and regional wall motion. Recent technical advances include the development of computer programs for analyzing diastolic function, parametric imaging methods such as "phase" analysis and methods for calculating absolute ventricular volumes. Thallium-201 scans provide maps of regional myocardial perfusion. Recent advances include development of computer programs to quantitate regional thallium-201 uptake and to calculate thallium-201 turnover rates and the development of tomographic imaging systems. Technetium-99m pyrophosphate localizes in irreversibly damaged myocardium and provides a method for diagnosing, localizing and sizing acute myocardial infarcts. Recent applications include tomographic imaging to improve image contrast and development of criteria to identify high risk patients after infarction. Two important trends affecting the application of all the radionuclide studies in clinical cardiologic practice are the increasing use of decision analysis for incorporating results of multiple tests into single diagnostic probability statements, and the use of diagnostic algorithms that include the radionuclide studies to optimize the cost effectiveness of evaluation of patients with ischemic heart disease.

Coronary Angiography↗

The genetics of malignant melanoma: lessons from mouse and man.

Therapeutic resistance and proclivity for metastasis are hallmarks of malignant melanoma. Genetic, epidemiological and genomic investigations are uncovering the spectrum of stereotypical mutations that are associated with melanoma and how these mutations relate to risk factors such as ultraviolet exposure. The ability to validate the pathogenetic relevance of these mutations in the mouse, coupled with advances in rational drug design, has generated optimism for the development of effective prevention programmes, diagnostic measures and targeted therapeutics in the near future.

Animals↗

Prevention and management of CMV-related problems after hematopoietic stem cell transplantation.

Prevention and management of human cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation has improved substantially in the past decade. However, with this improvement, there is increased complexity in deciding which diagnostic tests, treatment strategies and immunologic assessments are optimal for different patient populations. The purpose of this review is to address certain practical problems that commonly arise and suggest a suitable approach to management that should have wide applicability.

Acyclovir↗