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Biodistribution properties of (111)indium-labeled C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid humanized 3S193 diabody and F(ab')(2) constructs in a breast carcinoma xenograft model.

The humanized complementarity determining region-grafted anti-Lewis Y (Le(y)) monoclonal antibody [humanized 3S193 (hu3S193)] was developed for targeting Le(y)-expressing epithelial tumors such as breast, colon, lung, prostate, and ovarian carcinoma. We are exploring the potential use of smaller molecular size, bivalent analogues of hu3S193, because the faster blood clearance of M(r) approximately 54,000 diabody and M(r) approximately 110,000 F(ab')(2) molecules may be advantageous in achieving optimal and rapid tumor uptake for diagnostic and potential therapeutic applications. The single-chain variable fragment-5 residue linker construct (diabody) was expressed using the bacterial secretion vector pPOW3, and soluble product was purified without refolding processes. The F(ab')(2) fragment was obtained by pepsin digest of parental hu3S193. To facilitate evaluations, the radiometal (111)In was used to label C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid chelated diabody and F(ab')(2). The immunoreactivity of the radiolabeled constructs was 41.3 and 58.6%, and the K(a) was 1.68 x 10(6) M(-1) and 5.33 x 10(6) M(-1) for the diabody and F(ab')(2), respectively. Radioconjugates were injected into mice bearing Le(y)-positive MCF-7 tumors, and biodistribution properties were determined at various time points after injection. The uptake of radiolabeled diabody in xenografts was maximal at 1 h after injection (4.7 +/- 0.6% injected dose/g), whereas the F(ab')(2) peaked at 8 h after injection (14.2 +/- 2.4% injected dose/g). The tumor:blood ratio at 4 h for the diabody and F(ab')(2) was 5:1 and 2:1, which increased to 20:1 and 5:1, respectively, at 8 h and increased further to 40:1 and 130:1, respectively, at 48 h. These results demonstrate that the diabody construct may have applications as a diagnostic imaging reagent, whereas F(ab')(2) displayed effective tumor targeting and may have potential as a therapeutic molecule in patients with Le(y)-expressing tumors.

Animals↗

[Mesenteric localization of thrombosis in the antiphospholipid syndrome].

The authors describe a thrombophil condition manifested at an atypical site--partial thrombosis of the sup. mesenteric vein. The diagnosis was made during surgery followed by haemocoagulation examination which repeatedly revealed positive lupus anticoagulans (LA). Early diagnosis of the acute state with initiation of anticoagulant treatment and solution of the diagnostic conclusion--antiphospholipid syndrome--make an optimal therapeutic procedure possible.

Antiphospholipid Syndrome↗

Diagnosis of pulmonary embolism.

No single noninvasive test for pulmonary embolism is both sensitive and specific. Some tests are good for "ruling in" pulmonary embolism (e.g., helical CT) and some tests are good for "ruling out" pulmonary embolism (e.g., D-dimer); others are able to do both but are often nondiagnostic (e.g., ventilation-perfusion lung scanning). For optimal efficiency, choice of the initial diagnostic test should be guided by clinical assessment of the probability of pulmonary embolism and by patient characteristics that may influence test accuracy. This selective approach to testing enables pulmonary embolism to be diagnosed or excluded in a minimum number of steps. However, even with the appropriate use of combinations of noninvasive tests, it is often not possible to definitively diagnose or exclude pulmonary embolism at initial presentation. Most of these patients can be managed safely without treatment or pulmonary angiography by repeating ultrasound testing of the proximal veins after one and 2 weeks to detect evolving deep vein thrombosis. Helical CT and MRI are rapidly improving as diagnostic tests for pulmonary embolism and are expected to become central to its evaluation.

Algorithms↗

Treatment of hepatitis B reinfection after liver transplantation.

Patients with chronic replicative hepatitis B virus (HBV) infection who undergo orthotopic liver transplantation (OLT) in the absence of prophylactic antiviral therapy have a high risk of graft reinfection. Serial monitoring of serum HBV DNA and HBV sequence analysis, especially of the polymerase and the "a" epitope of the surface antigen, may be a requisite diagnostic tool in order to provide optimal therapeutic management for inhibition of viral replication before and after OLT. Combination therapy with hepatitis B immunoglobulin (HBIG) and lamivudine has been widely adopted as an effective prophylactic treatment regimen against recurrent HBV disease. The major issue of concern has been the development of lamivudine resistance due to the emergence of mutations in the YMDD motif of the HBV DNA polymerase gene. Among newer antivirals, adefovir dipivoxil and entecavir have been demonstrated to be effective against both wild-type and lamivudine resistant mutants. Due to the availability of antiviral drugs, outcome of patient and graft survival has dramatically improved and has become similar or even better as compared to patients with non-HBV-related liver diseases.

Drug Therapy, Combination↗

[Osteoporosis--prevention, diagnosis and treatment. A systematic literature review. SBU conclusions and summary].

A report by the Swedish Council on Technology Assessment in Health Care (SBU) has reviewed, classified, and graded the scientific literature on prevention, diagnosis and treatment of osteoporosis. This article summarizes the overall conclusions. There is no scientific evidence to support the use of bone density measurement as a screening method in healthy, middle-aged individuals. Patients with osteoporosis-related fractures are an undertreated group as regards pharmacotherapy and other interventions to prevent new fractures. There are some evidence that physical exercise to reduce falls among elderly and hip protectors can prevent fractures. The combination therapy of calcium and vitamin D is shown to reduce the risk for hip fractures and other fractures except vertebral fractures in elderly women. Bisphosphonates are shown to reduce the number of fractures, mainly vertebral fractures. SERM is shown to reduce the risk for vertebral fractures in postmenopausal women with osteoporosis. Important risk factors for osteoporosis-related fractures that can be treated are physical inactivity, low weight, tobacco smoking, high alcohol consumption, tendency to fall, impaired vision, low exposure to sunlight, and use of corticosteroids. No particular diagnostic method or measurement site is optimal for determining the risk for fracture in all parts of the skeleton. The various measurement methods--dual energy x-ray absorbtiometry (DXA), ultrasound (QUS), and computed tomography (QCT)--are not directly comparable.

Aged↗

[To delay may be wise].

We report a case of acute renal failure, quickly evolved, in which the coexistence of parenchimal nephropaty and renal mass, have induced not a common diagnostic and therapeutic approach, finalized to optimize the interventional nephrology procedures, with the use of various imaging procedures. It is followed a multidisciplinar therapeutic approach, with the employment of dialysis, steroid therapy and surgical treatment.

Acute Kidney Injury↗

B-type natriuretic Peptide and the diagnosis of acute heart failure.

Heart failure is a major public health problem and despite significant advances in treatment remains the only cardiovascular disease still on the rise. Because this patient population often has a number of other concomitant diseases, including hypertension, coronary artery disease, arrhythmias, diabetes, chronic obstructive pulmonary disease, and renal insufficiency, diagnosis can be difficult. Currently, diagnosis of acute decompensated heart failure (ADHF) relies largely on patient history, signs, and symptoms. Rapid and accurate diagnosis of ADHF in the emergency department (ED) is essential for timely initiation of treatment. Thus, any means for improving the speed and accuracy of ADHF diagnosis in the ED can contribute to better clinical and economic outcomes. Measurement of circulating endogenous B-type natriuretic peptide (BNP) has proven to be a sensitive and specific test for heart failure that can easily be used in the ED. Used in conjunction with standard diagnostic procedures, measurement of BNP levels can improve the accuracy of ADHF diagnosis during the critical window for optimal care.

Decision Trees↗

[Future organisation of colorectal cancer surgery in Denmark].

We recommend that in the future, surgery for colorectal cancer (CRC) in Denmark should be done in 10 to 15 colorectal units with an uptake zone of 350,000-500,000 citizens each. These units should perform both acute and elective CRC surgery and acute surgical treatment of other intestinal diseases. In each unit, a senior colorectal surgeon should be available on a 24-hour shift, and there should be sufficient diagnostic and theatre capacity to ensure optimal treatment levels. A stoma clinic should be available Monday to Friday. The units should perform research according to international standards. Each senior surgeon should document his or her relevant continuing surgical education. A national postgraduate education should be ensured to all members of the multidisciplinary team according to the standards in force in Great Britain. The treatment of primary advanced T4 tumors and local recurrence should be done in only one to two colorectal units in Denmark, and the treatment of local recurrence with spread to the pelvis should be done in only one unit in Denmark.

Clinical Competence↗

[Echinococcus granulosus--diagnostics and therapy problems--case report].

The case report of patient with asymptomatic liver echinococcosis several year observing was shown. The liver cyst occasionally revealed by ultrasound examination had doubled its diameter in two years, serological test result had suggested Echinococcus granulosus infection. After the initially treatment with benzimidazole the curative surgery had been conducted and histological examination confirmed the liver echinococcosis diagnosis. The headaches in two years after surgery needed the central nervous system echinococcosis considering in differential diagnostics. Because of the normal liver parenchyma ultrasound image, normal laboratory tests results and negative serological tests results the patient was considered as completely recovered after several year of observation. On the base of procedure undertaken the diagnostics and therapeutic possibilities were reviewed. The necessity of taking the echinococcosis into account in occasionally found liver cysts differential diagnostics and individual choice of the optimal therapeutic schema was underlined.

Albendazole↗

[Breast-conserving therapy in breast carcinoma--the indications and sequelae. The results of a multidisciplinary consensus meeting].

A multidisciplinary consensus development conference on the management of breast-preserving treatment in early breast cancer was organized in November 1989 in Berlin. Following a two-day discussion of data presented, conclusions and recommendations were achieved on the indication and limitation of breast conservation, the optimal technique as well as the diagnostic requirements and therapeutic strategies in context with breast conservation including follow-up.

Antineoplastic Agents↗

[Therapy of elderly cancer patients from the viewpoint of the radiologist].

For elderly cancer patients radiology is of importance in diagnosis and predominantly in therapy. Non invasive diagnostic procedures, the basis for an optimal organ-saving plan of radiotherapy, are well tolerated by these patients. Prognosis, especially indication of curative or palliative radiotherapy, depend more on the general condition of health than the patient's age. Physiological alterations caused by age and concomitant diseases produce a certain risk of radiological side-effects, for which examples of the skin, lung and brain are given. Even though radiotherapy of elderly cancer patients can hardly be expressed by statistics, it often prolongs survival time and improves quality of life.

Aged↗

Lipase activity measured in serum by a continuous-monitoring pH-Stat technique--an update.

Using recent knowledge regarding the roles of colipase, bile acids, Ca2+, and emulsifiers, we optimized a previously published pH-Stat method for lipase (EC 3.1.1.3) activity measurements. The recommended assay conditions are: olive oil/triolein, 100 mL/L; sodium glycocholate, 35 mmol/L; Ca2+, 8.5 mmol/L; and colipase, 6.0 mg/L. The sample volume is 0.10 mL, the reaction pH 9.0, the temperature 30 degrees C, and the concentration of titrant 15 mmol/L. Hydroxypropyl methylcellulose, 20 g/L, replaces acacia as emulsifier to avoid inhibition by excess Ca2+. The standard curve is linear to greater than 4566 U/L. The reference interval with olive oil as substrate is 30-235 U/L. Lipase activities with triolein substrate are 9.9% greater than with olive oil. Interference by pancreatic carboxylesterase (EC 3.1.1.1) activity is inhibited by incubating the sample with diisopropylfluorophosphate. Results correlate well with those by the optimized SingleVial method of Boehringer Mannheim Diagnostics (r = 0.997) and the immunochemical assay of Beckman Instruments, Inc. (r = 0.995). Correlation with the aca method (E.I. DuPont de Nemours & Company) is less satisfactory (r = 0.892), probably owing to lack of colipase in the latter method.

Adult↗

The difficult asthmatic.

A poor therapeutic response may be explained by incomplete or erroneous diagnostic assessment, by failure to employ optimal drug doses and combinations, or by inadequate attention to the non-pharmacologic aspects of management. Poor compliance and counterproductive patient attitudes may need to be addressed. These problems and the approach to asthma concomitant with other diseases are discussed.

Asthma↗

[Primers for the nef gene in the diagnosis of HIV infection using the polymerase chain reaction].

A new system of primers and internal probe identifying the nef gene of HIV-1 was selected and tested for the laboratory diagnosis of HIV infection by means of PCR. The proposed primers and probe by their characteristics approached the optimal ones for PCR diagnosis. The diagnostic value of the above system was confirmed by the PCR analysis of blood samples from 29 patients including subjects with a doubtful diagnosis of HIV infection. The results of the PCR analysis using primers nef1/nef2 correlated with the results obtained by employing the widely used primers for the gag gene SK38/SK39 and attested to the high specificity and diagnostic efficiency of the proposed system.

Acquired Immunodeficiency Syndrome↗

MR arthrography: is it worthwhile?

Magnetic resonance (MR) arthrography is possible in any joint in which standard arthrography is performed. The diagnostic potential of this technique is optimized in the assessment of complex anatomical structures and intra-articular abnormalities that are difficult to visualize on conventional MR images. This paper presents the most common applications of MR arthrography in the shoulder, hip, knee, ankle, elbow and wrist, and explores the clinical indications in which MR arthrography adds the greatest benefit compared to standard arthrography and conventional MR imaging. Arthrographic MR images are most valuable in the evaluation of glenoid and acetabular labra, tendons of the rotator cuff, post-operative menisci, osteochondral fractures and loose bodies.

Humans↗

Surgical strategies for giant intracranial aneurysms.

Management strategies for giant intracranial aneurysms are presented. Safe treatment of these lesions requires a complete diagnostic evaluation preoperatively, selection of the optimal surgical approach, early vascular control of the aneurysm, and careful clipping technique. Important intraoperative adjuncts, such as skull-base surgical approaches, endovascular methods, and hypothermic circulatory arrest greatly facilitate the treatment of these lesions. Some giant aneurysms cannot be clipped directly and require alternative techniques, such as proximal parent artery occlusion, excision, or aneurysmorrhaphy. Bypass techniques are an important aspect of these alternative treatments. Giant aneurysms are the vascular neurosurgeon's greatest challenge, and well-designed surgical strategies are critical to their successful treatment.

Craniotomy↗