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Biomedical subjects

B Goldstein

Publications and source records attributed to B Goldstein.

At least 163 records · Page 9Linked to original sources

Osteomyelitis and septic arthritis in premature infant.

A premature infant girl was born at 26 weeks' gestation by normal spontaneous vaginal delivery. After suffering from anemia, hyperbilirubinemia, and respiratory distress syndrome, she developed Pseudomonas aeruginosa sepsis of the right knee at the age of 68 days. She was treated with daily knee aspirations, antibiotic joint instillation, and intravenous antibiotics, based on culture and sensitivity reports. Although the patient did not respond to this treatment for two weeks, surgical incision and drainage with continued intravenous antibiotics finally resulted in a complete cure of the infection and restoration of full range of motion of the knee joint.

Anti-Bacterial Agents↗

The utilization of cross-sectional anatomy in a surgical residency training program.

The education of students and residents in a surgical department involves a thorough knowledge of three-dimensional anatomical relationships in the body. In addition, the advances in new imaging modalities demand an in-depth study of cross-sectional anatomy by both students and residents. Traditionally, surgical training incorporated dissections of cadavers and the progressive involvement of the resident in the surgical theater. At the King/Drew Medical Center cross-sectional anatomy has been incorporated into the teaching program. The central focus of this instructional program utilizes problem-solving learning modules that emphasize important surgical and anatomical principles.LEARNING MODULES FOR EACH MAJOR REGION OF THE BODY WERE ESTABLISHED AND INCLUDE THE FOLLOWING: (1) serial cross sections, corresponding computerized tomographic scans and roentgenograms; (2) an atlas (cross sections), case histories, and examination questions; and (3) audiovisual presentation of the normal anatomy, the surgical principles involved, and a discussion of the examination questions. The serial cross sections were prepared at the King/Drew Medical Center.A selected case study is used to illustrate how the knowledge of three-dimensional anatomy can be critical in the evaluation and surgical plan of a patient. Entire learning modules of the thorax and abdomen were used.

Abdomen↗

Cross-linking of IgE-receptor complexes at the cell surface: a fluorescence method for studying the binding of monovalent and bivalent haptens to IgE.

We have developed a method for use in investigating factors controlling the binding and cross-linking by bivalent haptens of immunoglobulin E (IgE) bound to receptors on rat basophilic leukemia (RBL) cells. This method employs monoclonal anti-2,4-dinitrophenyl (DNP) IgE that is labeled with fluorescein-5-isothiocyanate (FITC), and it measures FITC quenching that accompanies DNP occupation of the antibody combining sites in a titration experiment. The validity of this approach is demonstrated using the monovalent hapten DNP-L-lysine. The affinity constant for this ligand obtained by the FITC quenching method is compared with those obtained with previously established methods: equilibrium dialysis and quenching of endogenous tryptophan for IgE in solution and [3H]-DNP-L-lysine binding to IgE on cells. The FITC quenching method has been used to carry out a detailed study of the binding of monovalent DNP-aminocapryol-L-tyrosine (DCT) and bivalent (DCT)2-cystine to FITC-IgE and its Fab fragments in solution. Intrinsic (K) and cross-linking (Kx) affinity constants are obtained by analyzing the binding curves in terms of simple equilibrium equations. With these DCT haptens the ability of this method to assess hapten binding and cross-linking of IgE bound to receptors on RBL cells is shown.

2,4-Dinitrophenol↗

Effect of preferential insertion of LDL receptors near coated pits.

Recent experiments suggest that low density lipoprotein (LDL) receptors on human fibroblasts are not inserted into the plasma membrane uniformly, as earlier experiments indicated, but are inserted into specialized regions, called plaques, where coated pits form. If the consequent reduction in the time required for LDL receptors to diffuse to coated pits were significant, this could alter conclusions drawn from previous calculations based on the assumption that LDL receptors are inserted uniformly. In particular, the conclusion could be wrong that diffusion of LDL receptors to coated pits is the rate limiting step in the interaction of cell surface LDL receptors with coated pits. Here we calculate the extent of the reduction in mean travel time of an LDL receptor to a coated pit, as a function of the plaque radius. We find that only if LDL receptor insertion is limited to a very small portion of the plasma membrane near coated pit sites is there a substantial decrease in the average time it would take an LDL receptor to diffuse to a coated pit. In order for preferential insertion of LDL receptors into plaques to cut the mean receptor travel time in half, plaques would have to take up no more than 10% of the cell surface area; to reduce the travel time by a factor of 10, plaques would have to cover only 2% of the cell surface, approximately twice the area covered by coated pits at 37 degrees C.

Animals↗

The time development of direct hemolytic plaques: implications for the binding of IgM to cell surface haptens.

We studied the time development of direct hemolytic plaques in thin layers containing either sheep red blood cells (SRBC) directly haptenated (DH) with trinitrophenyl, or SRBC indirectly haptenated (IH) with dinitrophenyl coupled to human serum albumin. The DH-SRBC tend to be sparsely haptenated while the IH-SRBC tend to have very high local hapten densities. We observed marked differences in the growth of plaques for the two differently haptenated SRBC. Plots of the plaque radius squared vs time show that the slope of those curves that developed in a lawn of DH-SRBC tended to be constant while the slope of those curves that developed in a lawn of IH-SRBC tended to decrease with time. These results are what is predicted from theory if: IgM binds to DH-SRBC through attachments that rapidly dissociate, if IgM binds to IH-SRBC through attachments that very slowly dissociate, and if (3) both types of bound IgM can fix and activate complement.

Animals↗

Test of a theory relating to the cross-linking of IgE antibody on the surface of human basophils.

Recent mathematical models of bivalent hapten-induced histamine release from basophils predict that under appropriate conditions histamine release is maximum when cross-link formation is maximum, at a hapten concentration equal to 1/(2Ka), where Ka is the average affinity constant of the hapten for a single IgE binding site. To test this prediction we sensitized human basophils with a monoclonal anti-dinitrophenol IgE and generated histamine release dose-response curves with a bivalent hapten, alpha, epsilon-DNP-lysine. The monoclonal IgE has a published affinity constant of 7.1 X 10(7) M-1 for epsilon-DNP-lysine as determined by equilibrium dialysis. From the position of the maximum of the histamine dose-response curves, both in the presence and in the absence of monovalent DNP hapten, we determine that the sensitizing IgE has an intrinsic affinity constant of 6.9 +/- 0.5 X 10(7) M-1 for epsilon-DNP-lysine and 1.2 +/- 0.6 X 10(6) M-1 for alpha-DNP-lysine. The agreement between the two estimates of the epsilon-DNP-lysine affinity constant, one from histamine release experiments involving surface bound IgE and one from binding experiments involving IgE free in solution, 1) is consistent with a central prediction of the theory of cross-linking and 2) indicates that the hapten-binding properties of the IgE are unaffected by its being bound to Fc epsilon receptors on the basophil surface.

Basophils↗

Pseudo-outbreak of Bacillus species: related to fibreoptic bronchoscopy.

In July and August 1980, Bacillus spp. were isolated with unusual frequency from bronchial washings obtained during bronchoscopy performed with fibreoptic equipment. Clinical disease in culture-positive patients was not apparent; but Bacillus spp. were recovered from one component of the bronchoscope, the automatic suction valve. It appeared that secretions became contaminated during passage through the valve en route to a collection device. After institution of controls directed primarily at proper storage and maintenance, the number of isolations of Bacillus spp. decreased significantly. Thus, investigation revealed a site for contamination not previously described and the results suggest that in future outbreaks, cultures of the component parts may permit localization of the site of contamination which may help focus control measures.

Bacillus↗

Forward rate constants for receptor clusters. Variational methods for upper and lower bounds.

We are interested in the effect of receptor clustering on k+, the diffusion-limited forward rate constant for the binding of a ligand to a cell surface receptor. Here we estimate the reduction in k+ when receptors are clustered in various configurations. We obtain two alternative expressions for the flux of ligands into receptors distributed on a surface. Next we show through a variational principle that these provide both upper and lower bounds on the flux when evaluated for trial concentration functions which satisfy only the boundary conditions of the Laplace equation. We use an analogy with electrostatics to calculate rigorous bounds within approx. 10% of the exact result for a variety of planar clusters of hemispherical receptor sites. We also obtain an exact result for the flux into a spheroidal receptor and use this result to obtain bounds on the flux into certain receptor clusters.

Animals↗

Diffusion-limited forward rate constants in two dimensions. Application to the trapping of cell surface receptors by coated pits.

A variety of receptors are known to aggregate in specialized cell surface structures called coated pits, prior to being internalized when the coated pits close off. At 37 degrees C on human fibroblasts, as well as on other cell types, a recycling process maintains a constant number of coated pits on the cell surface. In this paper, we explore implications for receptor aggregation and internalization of the two types of recycling models that have been proposed for the maintenance of the coated pit concentration. In one model, coated pits alternate between accessible and inaccessible states at fixed locations on the cell surface, while in the other model, coated pits recycle to random locations on the cell surface. We consider receptors that are randomly inserted in the membrane, move by pure diffusion with diffusion coefficient D, and are instantly and irreversibly trapped when they reach a coated pit boundary (the diffusion limit). For such receptors, we calculate for each of the two models: the mean time tau to reach a coated pit, the forward rate constant k+ for the interaction of a receptor with a coated pit, and the fraction phi of receptors aggregated in coated pits. We show that for the parameters that characterize coated pits on human fibroblasts, the way in which coated pits return to the surface has a negligible effect on the values of tau, k+, and phi for mobile receptors, D greater than or equal to 1.0 X 10(-11) cm2/s, but has a substantial effect for "immobile" receptors, D much less than 1 X 10(-11) cm2/s. We present numerical examples to show that it may be possible to distinguish between these models if one can monitor slowly diffusing receptors (D less than 1 X 10(-11) cm2/s) on cells whose coated pits have relatively short lifetimes (less than or equal to 1 min). Finally, we show that for the low-density lipoprotein (LDL) receptor on human fibroblasts (D = 4.5 X 10(-11) cm2/s), the predicted and observed values of K+ and phi are in close agreement. Therefore, even for slowly diffusing LDL receptor, unaided diffusion as the transport mechanism of receptors to coated pits is consistent with measured rates of LDL internalization.

Coated Pits, Cell-Membrane↗

Equilibrium theory for the clustering of bivalent cell surface receptors by trivalent ligands. Application to histamine release from basophils.

For certain cell types, the cross-linking of bivalent cell surface receptors by multivalent ligands is an important biochemical step in the transmission of information across the cell's membrane to its interior. The formation of cell surface receptor-ligand aggregates has been shown to "turn on" and "turn off" particular cell responses. It has been hypothesized that very large aggregates generate signals that small aggregates cannot. This hypothesis has not been rigorously tested as yet, in part because of a lack of quantitative information about aggregate sizes. Here we develop a general equilibrium theory for the clustering of bivalent receptors by trivalent ligands. In addition to predicting the concentrations of receptor-ligand aggregates of all possible sizes, we show that a range of ligand concentrations exists at which extremely large aggregates, i.e., superaggregates, form on the cell surface. The formation of a superaggregate corresponds to a sol-gel phase transition, and we study this transition in some detail. For the biologically interesting case of histamine release by basophils, we show, using realistic parameter values, that such transitions should occur when the cells are from highly allergic individuals. We prescribe in detail experimental conditions under which such transitions should occur. These conditions can be used as a guide to test whether or not large aggregates provide signals to cells that small aggregates do not.

Animals↗

Approach to quality assurance in an emergency department: a one-year review.

The Joint Commission on Accreditation of Hospitals requires that an organized quality assurance program be in place for all emergency departments under its review. The authors' institution has had a quality assurance program since 1978. The program is structured to assess medical records against pre-established standards of medical care; to review all radiologic, electrocardiographic and bacteriologic culture reports to avoid discrepancies following initial clinical intervention; and to analyze all emergency department deaths. A review of this program was undertaken for the year 1982 to assess outcome and benefit. Of 74,760 charts reviewed, 744 did not meet the pre-established standards. Seventy-seven patients were asked to return to the emergency department at once. Three hundred fourteen radiographs were initially misread by clinicians and 63 patients were called back for immediate reexamination. Seventy-four electrocardiograms were initially misinterpreted, and 21 patients required urgent call-back. One hundred eighteen patients with positive urine cultures and 35 patients with positive throat cultures were not treated or were incorrectly treated during their initial visit. These patients were notified of the need for additional therapy. There were 158 emergency department deaths, and 11 were thought to have been possibly preventable.

Emergency Service, Hospital↗

Pleural biopsy. A report of 750 biopsies performed using Abrams's pleural biopsy punch.

We present the results of 750 consecutive pleural biopsies performed with the Abrams pleural biopsy punch to indicate the effectiveness, safety and ease of the procedure. The biopsies were performed by 27 members of our medical staff. Pleural tissue was obtained in 90% of the biopsy specimens taken from patients with pleural effusions and in 79% of those taken in the absence of pleural fluid. These 'dry' biopsies were restricted to those operators with a minimum experience of 50 previous biopsies. Inclusion of tissue other than pleura occurred more frequently in the 'dry' biopsies (16.6%) than in those with pleural fluid (0.8%). There were no complications which required intervention. The problem of 'idiopathic' pleural disease is discussed. We emphasize the biopsy technique and the need for a constant and interested histologist.

Biopsy, Needle↗

A comparison of the effects of exposure of baboons to crocidolite and fibrous-glass dusts.

Epidemiological studies have not revealed any significant health hazards from exposure to fibrous glass and animal experiments have been inconclusive. Baboons exposed to a fibrous-glass dust cloud with size features similar to those of crocidolite asbestos developed focal peribronchiolar fibrosis with scant ferruginous body formation. The lesions were similar to those produced by crocidolite but were less extensive. No neoplasms occurred.

Animals↗

The effect of receptor clustering on diffusion-limited forward rate constants.

The effect of receptor clustering on the diffusion-limited forward rate constant (k+) is studied theoretically by modeling cell surface receptors by hemispheres distributed on a plane. We give both exact results and bounds. The exact results are obtained using an electrostatic analogue and applying the method of the images. Accurate upper bounds on k+ are found from a variational principle.

Cell Membrane↗

Dendritic vacuolization in the central nervous system of rats after long-term voluntary consumption of ethanol.

Adult male rats were housed in a colony environment for six months, with ad lib access to anise-flavored 10% ethanol in water. Animals were then removed from the colony, and their consumption of alcohol during a period in isolated housing was measured. Individual rats were scored as high, moderate, and low consumers. Animals from each scoring category were killed for light and electron microscopic study of central nervous system tissue. High consumers frequently displayed varicose distortions of the dendritic profiles, with internal membranous vesicles. Such abnormalities were rarely found in dendrites of low-ethanol-consuming colony mates. The dendritic vacuoles often appeared empty and membrane-limited. Some vacuoles contained membranous inclusions. Dendrites which displayed electron-lucent cavities without membranous limits or contents were also found. Some invaginations of dendritic membranes were identified. The possible sequential relationship between these forms of dendritic alterations could not be determined. Some neuron cell bodies displayed vacuolar inclusions as well. Dendritic and somatic abnormalities were found in cerebral and cerebellar cortices, hippocampus, mammillary bodies, and the periaqueductal gray matter of the brain stem.

Alcoholic Intoxication↗