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Biomedical subjects

L S Zuckier

Publications and source records attributed to L S Zuckier.

At least 37 records · Page 2Linked to original sources
PubMed1995

Premature extravasation. A bleeding site identified during the dynamic phase of Tc-99m red blood cell bleeding scintigraphy.

Tc-99m RBC scintigraphy is favored by many investigators because it provides the ability to image the abdomen over a prolonged period of time, thereby allowing identification of delayed bleeding sites that are frequently encountered due to the intermittent nature of gastrointestinal bleeding. The authors describe a case of bleeding scintigraphy with labeled red blood cells in which the bleeding site was identifiable only on the dynamic blood-flow and first static images. On later images, the labeled blood cells had spread throughout the colon, rendering localization of the actual bleeding site impossible. Two previous red blood cell scintigraphies and a subsequent contrast angiogram did not reveal sites of active bleeding. As illustrated by this unusual case, factors governing timing and visualization of abnormal bleeding sites are discussed, as is a differential diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding scintigraphy.

Adult↗
PubMed1995

Accuracy of measurement of dual-isotope Schilling test urine samples: a multicenter study [corrected].

UNLABELLED: As a component of our quality assurance program, this multicenter study was performed to characterize the magnitude and types of error present in measurement of typical dual-isotope Schilling test (DIST) urine samples. METHODS: A panel of three simulated DIST urine samples was formulated corresponding to diagnoses of normal excretion, malabsorption and pernicious anemia and was distributed to eight hospitals in our regional area (three novice and five experienced users). Count-rate data and urine volume measurements from each site were analyzed for accuracy against the predicted values and a carefully measured gold standard and were correlated with the methodology and equipment used. RESULTS: Three of 24 results were uninterpretable due to an overly low ratio of intrinsic factor bound to free vitamin B12 excretion (B/F ratio), inconsistent with possible diagnoses. In 20 of 21 interpretable samples, results corresponded to the appropriate diagnoses, with typical values noted in 18 of the cases and slightly atypical yet diagnostic values seen in the remaining two cases. In only one sample did values correspond to an erroneous diagnosis (low normal or partial malabsorption rather than pernicious anemia). The four major discrepancies (test failure or misdiagnosis) were largely attributable to blunders and were limited to two of the three novice sites and to a single experienced site which had grossly inaccurate raw data (background greater than sample counts). CONCLUSION: Quantitation of vitamin B12 excretion in DIST urine samples is a reliable method of evaluation when performed by reasonably experienced and competent clinical laboratories. Improved accuracy may be obtained by increasing the stochastic certainty of the count data and by more careful measurement of the sample and urine volumes.

Anemia, Pernicious↗
PubMed1995

A nonimaging scintillation probe to measure penile hemodynamics.

UNLABELLED: We have developed a penile nonimaging scintillation (PNIS) probe consisting of a plastic well-type scintillation crystal interfaced to a portable computer and acquisition board. This report describes the design of the PNIS probe, performance characteristics, mode of usage and illustrative results which demonstrate its capabilities. METHODS: With the PNIS probe, penile blood-pool studies were performed in nine patients utilizing 3.7 MBq (100 microCi) autologous 99mTc-labeled red blood cells (RBCs). Venous blood standards were assayed to enable conversion of the count rate to volummetric measurements. Washin of peripherally administered 99mTc-RBCs was mathematically analyzed to estimate penile blood volume and cavernosal flow rate in the flaccid state. The rate of change of penile blood volume after intracavernosal vasodilators was used to generate measures of stimulated flow. RESULTS: A major advantage of this device over the gamma-camera is a 3300-fold increase in count rate sensitivity, which allows for markedly improved temporal resolution while significantly reducing the radiopharmaceutical dosage. Additionally, the PNIS probe is portable, economical and is not dependent on operator-defined regions of interest. Count rate sensitivity is relatively constant within the bore, with the exception of the proximal region adjacent to the opening, where geometric efficiency is reduced. CONCLUSION: The PNIS probe is an effective device for measuring penile activity in radionuclide studies, allowing for acquisition of time-activity curves of the penis during flaccid washin of peripherally labeled red blood cells and after pharmacologic stimulation to induce erection.

Adult↗
PubMed1994

The use of severe combined immunodeficiency mice to study the metabolism of human immunoglobulin G.

BACKGROUND: Although the four human immunoglobulin G (IgG) isotypes are similar in structure, they exhibit significant differences in effector function and catabolic half-life. With advent of structurally engineered antibodies, there is the potential to design antibody constructs with desired half-lives; however, it is first necessary to discover the structures and mechanisms that control immunoglobulin metabolism. METHODS: Radioiodinated chimeric antibodies, consisting of a mouse antidansyl variable region and the four human IgG constant regions, were injected intravenously into Balb/c and severe combined immunodeficiency (SCID) mice, and their half-lives were determined by whole body and whole blood counting. Dependence of the rate of immunoglobulin catabolism on immunoglobulin concentration, a normal regulatory phenomenon specific to IgG, was evaluated by the introduction of large amounts of human gamma-globulin intraperitoneally. RESULTS: Whole body and blood half-lives were statistically indistinguishable. The four IgG isotypes were eliminated from the whole animals in a predominantly single-phasic manner, with the half-life being dependent on the isotype studied. In Balb/c mice, immune elimination frequently occurred after 6 days, although this was not observed in SCID mice. Relevance of the model was confirmed by the demonstration of the presence of the concentration-catabolism phenomenon, a relationship unique to normal IgG regulation. CONCLUSIONS: SCID mice provide an adequate initial animal model for the study of human-mouse chimeric antibodies. Further understanding of the factors governing immunoglobulin catabolism can be probed by study of recombinant human constant regions in this animal system.

Animals↗
PubMed1994

Expression of human tumor mucin-associated carbohydrate epitopes, including sialylated Tn, and localization of murine monoclonal antibodies CC49 and B72.3 in a syngeneic rat colon carcinoma model.

Using immunohistochemical techniques and whole-cell enzyme-linked immunosorbent assay, we have determined that monoclonal antibodies (mAbs) B72.3 and CC49, which are widely used in the diagnosis and treatment of several human epithelial cancers, are expressed in a transplantable rat colon carcinoma cell line, K12-TRb. MAbs B72.3 and CC49 react with tumor-associated glycoprotein-72 (TAG-72) which is a carcinoma mucin molecule expressed in colon, breast, pancreatic, ovarian, lung, and gastric cancers. The carbohydrate epitope for mAb B72.3 is sialylated Tn (sTn), whereas CC49 reacts with an unknown carbohydrate epitope. K12-TRb is a transplantable rat colon carcinoma cell line derived from a dimethylhydrazine tumor which grows as progressive tumors in syngeneic BD IX rats. We found that the carbohydrate epitopes for mAbs B72.3 and CC49, including sTn, were more tumor-restricted in the rat than in humans. The only binding these had mAbs to normal rat tissue was to small-intestinal mucosa. MAbs B72.3 and CC49 were radiolabeled with iodine-125 (125I) and injected intravenously into BD IX rats containing subcutaneously grown syngeneic K12-TRb tumors. Biodistribution experiments were conducted by dissecting groups of three rats on days 2, 4, 7, and 14 after injection of radiolabeled mAbs. These experiments confirmed that maBs B72.3 and CC49 localize to K12-TRb tumors in vivo, and that the higher affinity mAb CC49 localized better than mAb B72.3. Gamma-camera imaging of subcutaneous K12-TRb tumors was successfully performed using 125I-labeled mAb CC49. The importance of this model is that mAbs B72.3 and CC49, immunoconjugates of these mAbs, and vaccines containing their corresponding carbohydrate epitopes, including sTn, can be studied in a relevant immunocompetent syngeneic rat colon carcinoma model.

Animals↗
PubMed1994

Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B.

The therapeutic efficacy of the immunoglobulin G1 (IgG1) monoclonal antibody (MAb) 2H1 to the Cryptococcus neoformans capsular polysaccharide was studied with and without amphotericin B (AmB) in a murine model of intravenous (i.v.) infection. MAb and AmB were administered by intraperitoneal (i.p.) injection after i.v. infection with a C. neoformans serotype D strain. Intraperitoneal administration of MAb 2H1 resulted in rapid distribution to the intravascular compartment, and the half-lives of i.p. and i.v. administered MAb were similar. Administration of MAb 2H1 alone resulted in increased survival, decreased lung fungal burden, and reduced serum glucuronoxylomannan antigen levels when given 2 to 6 h but not 24 h after infection. In vivo, the combination of MAb 2H1 and AmB was more effective at prolonging survival than either agent alone. MAbs of IgM, IgG1, IgG3, and IgA isotypes given 1 day after infection were effective in reducing serum GXM-D levels, with their relative efficacy being IgG1 > IgG3 > IgM > IgA. In vitro, MAb 2H1 was a potent opsonin of C. neoformans and the combination of MAb 2H1 and AmB was more effective than either agent alone in decreasing C. neoformans colony counts in the presence of the murine macrophage cell line J774.16. The results confirm that capsule-binding MAbs can enhance the effect of AmB against C. neoformans and provide support for considering combined therapy in humans.

Amphotericin B↗
PubMed1993

The role of nuclear medicine in the evaluation of the male genital tract.

Scintigraphic techniques for evaluation of impotence are still evolving. Blood pool studies are most useful in assessing the integrity of arterial inflow, but may also be used to generate indices of venous leak. A non-imaging version of this test may represent a simple and cost-effective alternative. Washout of intracavernosal xenon during erection seems the most useful method of testing venous integrity. Washout using Tc-RBC may emerge as a convenient alternative to the more technically difficult xenon examinations. Development of more effective pharmacologic stimuli may further improve the utility of this quantitative and physiologic examination.

Erectile Dysfunction↗
PubMed1992

Nuclear medicine in problems of fertility and impotence.

Nuclear medicine techniques may be used to test fallopian tube patency and penile vascular inflow and outflow. Radionuclide hysterosalpingography (HSP) is a readily performed method of evaluating fallopian tube patency, and is believed to be more physiologic and functionally informative than the accepted radiologic method of contrast HSP. The test is simple to perform and interpret and offers an accurate alternative to the contrast examination. For scintigraphic evaluation of impotence, blood pool studies are most useful in assessing the integrity of arterial inflow, but may also be used to generate indices of venous leak. Washout of xenon after subcutaneous injection, in the flaccid state, has been used as a measure of baseline penile perfusion, as has intracavernosal injections in the flaccid penis. Intracavernosal xenon washout during erection seems the most useful method of testing venous integrity. Washout using technetium-99m (99mTc)-labeled red blood cells (99mTc-RBC) may emerge as a convenient alternative to the more technically difficult xenon examinations.

Erectile Dysfunction↗
PubMed1990

Current state of the hybridoma technology.

The first description of the hybridoma technology in 1975 seemed to hold enormous promise for the treatment of a variety of human disease. The ability to produce monoclonal antibodies led to the availability of large amounts of homogeneous and predictable preparations of antibody. The potential to renew indefinitely a particular antibody surmounted many of the technical and regulatory problems that made polyclonal antisera difficult to use as therapeutic agents in man. The hybridoma technology seemed even more valuable as it became clear that it could lead to the generation of pure, highly specific antibodies from impure, poorly characterized antigens. Monoclonal antibodies have been extremely useful in basic investigations and have facilitated the development of new diagnostic tests for serum and tissue components and infectious agents. However, novel approaches are needed in order to provide more useful, less immunogenic antibodies which could be used routinely for passive immunization in the treatment of infections or for tumor targeting.

Animals↗
PubMed1990

Testicular scanning and other applications of radionuclide imaging of the genital tract.

The major application of nuclear imaging techniques to the genital tract is pertechnetate scintigraphy for evaluation of the acute hemiscrotum. Within a few years of the first descriptions of scrotal imaging, this technique achieved recognition as a valuable, even indispensable, emergency diagnostic procedure in this context; its validity has since been well confirmed in hundreds of reported cases. Because it is an established procedure with widely recognized applications, its discussion will occupy most of this article. Other nuclear procedures, less widely used either because they are investigative or applicable to smaller patient populations, will be more briefly described.

Diagnosis, Differential↗
PubMed1990

Technetium-99m antimony sulphide colloid lymphoscintigraphy of the prostate by direct transrectal injection.

Laterality of prostatic lymphatic drainage was successfully assessed in nine patients with prostatic carcinoma after direct unilateral transrectal injections of 99Tcm-antimony sulphide colloid by Franzen needle. Pelvic lymphatic drainage was equally divided between ipsilateral, contralateral and bilateral patterns. The frequent observation of radiocolloid migration to contralateral lymph node groups in patients with prostate carcinoma, including those with primary disease localized clinically to a single lobe of the prostate, indicates the potential for contralateral pelvic lymph node metastases in this population. This finding may be important in determining the appropriate surgical staging and treatment of patients with prostate carcinoma. The clinical applicability of lymphoscintigraphy in the evaluation of metastatic spread and in lymph node biopsy planning requires further study.

Administration, Rectal↗
PubMed1990

Incidental abnormalities detected during scintigraphy for gastrointestinal bleeding.

The authors describe a number of abnormalities that were incidentally found in a series of 132 scintigraphic studies performed for acute gastrointestinal hemorrhage. These incidental abnormalities involved the vascular system, reticuloendothelial system, and soft tissues. Correlative radiographs and computed tomographic scans are presented for some cases. The authors explore the potential impact of these abnormalities on subsequent patient evaluation and care, including radiologic workup.

Adult↗
PubMed1989

Immunologic and pharmacologic concepts of monoclonal antibodies.

While monoclonal antibodies have solved many of the difficulties of using immunologic reagents for radioimmunodiagnosis and therapy, in the 13 years since their introduction a number of persistent problems remain, most notably a low yield of antibody-producing cells from the fusion process, difficulty in obtaining high-affinity antibodies, and the potential immunogenicity of murine immunoglobulins (Igs). Several solutions are under development, including fusion techniques that enrich for cells producing desired antibodies, production of human-mouse chimeric antibodies by recombinant DNA technology, and the generation of human monoclonal antibodies by promising new approaches. Until these upcoming methodologies are established, and to better direct their development and application, a sound understanding of the pharmacology of presently available native and modified monoclonal antibodies is crucial. Although much has been already determined in this area, a great deal of further clarification remains necessary.

Animals↗
PubMed1988

Fraley's syndrome: case report and update on current diagnostic methods.

A 38-year-old woman presented with fever, right flank pain, and a clinical diagnosis of pyelonephritis. Work-up revealed the presence of a crossing arterial branch causing obstruction of the superior infundibulum of the right kidney, which is an uncommon cause of nephralgia and urinary infection initially described by Fraley in 1966. Intravenous urography, retrograde pyelography, and angiography remain the mainstay of diagnosis, much as in the initial descriptions of this entity. [131I]Hippuran imaging, with analysis of the upper and lower pole regions of interest, provides a simple yet powerful method of evaluating functional and excretory changes in the superior infundibulum, and has proved more efficacious than previously reported whole-kidney renograms. Renal scintigraphy represents a relatively noninvasive method of serial functional examination in this disorder. Ultrasound imaging, by monitoring upper-pole dilatation, may provide complementary morphologic information important for long-term follow-up.

Adult↗