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Biomedical subjects

B Mandell

Publications and source records attributed to B Mandell.

16 recordsLinked to original sources

Clinical and subclinical ophthalmic findings with retinol deficiency.

BACKGROUND: Patients at risk for retinol deficiency in developed countries include those with hepatic dysfunction and malabsorption states. Symptoms of retinol deficiency may go unrecognized or unreported. METHODS: The authors describe 15 patients with hepatic dysfunction, two of whom had procedures that would predispose to malabsorption and were ophthalmologically symptomatic of retinol depletion. The other 13 patients were ophthalmologically asymptomatic liver transplant candidates examined prospectively for subclinical evidence of retinol deficiency. Combined laboratory analysis, Schirmer's testing, conjunctival impression cytology, and electroretinography were performed. RESULTS: Twelve of 15 patients had serum retinol levels below the lower limit of normal. Aqueous tear production was reduced in 7 of 14 patients. Abnormal conjunctival morphology was noted in 6 of 12 patients. Electroretinograms were abnormal in the two patients who were visually symptomatic and in seven of nine patients who were ophthalmologically asymptomatic. CONCLUSION: Subclinical, physiologically significant retinol deficiency may be a frequent and unrecognized problem among patients with hepatic dysfunction.

Adolescent

Diode-laser photocoagulation for zone 1 threshold retinopathy of prematurity.

We used the diode-laser indirect ophthalmoscope in the treatment of 17 (30 eyes) infants with zone 1 (a circle centered on the optic disk with a radius of twice the distance from the disk to the fovea) threshold retinopathy of prematurity (at least five continuous or eight cumulative 30-degree sectors [clock hours] of ridge with extraretinal fibrovascular proliferation in the presence of plus disease). Mean follow-up was 31.2 weeks. Two eyes (6.7%) required retreatment of missed areas that had persistent plus disease (enlarged posterior veins and tortuous arterioles). A favorable outcome was attained in 25 eyes (83.3%). Five eyes (16.7%) developed retinal detachments, three of which remained stable at Stage 4A (extrafoveal retinal detachment) and two of which ultimately progressed to Stage 5 (total retinal detachment). Both eyes that went on to Stage 5 had severe posterior pole hemorrhages at the time of treatment. Two eyes that developed retinal detachments (one, stage 4A and one, stage 5) had rhegmatogenous components. Among 14 infants followed up for more than three months, four developed nystagmus, and six developed strabismus. In contrast to cryoablation, diode-laser photoablation of the peripheral retina was found to be an effective treatment for threshold retinopathy of prematurity located in zone 1. Portability and ease of use of the laser system, precision of treatment, and minimal postprocedural adnexal inflammation are further advantages of this therapeutic modality.

Female

Cerebral blood flow in systemic lupus erythematosus with or without cerebral complications.

We measured mean cerebral blood flow (CBF) in 25 lupus patients using the xenon-133 method. The CBF was normal in lupus patients without cerebral disease and also in CNS lupus patients in remission. The CBF was lower than normal during bouts of cerebral lupus (p less than 0.001). Repeat studies showed a stereotyped pattern consisting of depressed CBF during exacerbation of CNS disease and normalization of CBF during remission (p less than 0.01). These results show that CBF is a sensitive indicator of activity of CNS disease and that the direction of change in CBF reflects the clinical course of CNS lupus.

Brain Diseases

Demonstration of calcium-dependent chemotactic factor activatable esterase activity in human neutrophils: relationship with chemotaxis and chemotactic deactivation.

An increase in esterolytic activity, as measured by [3H] BAEE hydrolysis, was demonstrated in human neutrophil suspensions following incubation with three distinct chemotactic factors. The increased activity was demonstrated in intact cells as well as in cell lysates. The FMLP-enhanced enzymatic hydrolysis of BAEE was found to be calcium dependent. Esterase activation by FMLP was maximal at 1.0 mM of added calcium. Similar dose-response curves for esterase activation, chemotaxis, and chemotactic deactivation were obtained with the chemotactic factor FMLP, suggesting that in human neutrophils all three functions utilize some of the same early molecular events following chemotactic factor binding to th neutrophil surface.

Arginine

Mechanism of action of colchicine in acute urate crystal-induced arthritis.

Phagocytosis of urate crystals by human or rabbit neutrophils induces the synthesis and release of a glycoprotein, the crystal-induced chemotactic factor (CCF), which is chemotactically active both in vitro and in vivo. It has been proposed that CCF is a prime mediator of the acute gouty attack. Colchicine has been shown to decrease the production and release of this factor in vitro. In these studies, colchicine, at nonleukopenic doses, is shown to abrogate the acute arthritis induced by monosodium urate crystals in rabbits, but to have no effect upon the arthritis induced by the injection of the purified cell-derived chemotactic factor. Serum colchicine levels were 0.48-0.58 muM at 30 min and 0.12-0.3 muM at 90 min after intravenous injection of 0.2 mg/kg colchicine. Peripheral blood polymorphonuclear leukocytes obtained from colchicine-treated animals migrated normally towards a chemotactic stimulus but failed to produce CCF after phagocytosis of monosodium urate crystals. The dialyzed synovial fluid from rabbits injected with microcrystalline sodium urate contained chemotactic activity that was not present when animals were also given intravenous colchicine or injected intra-articularly with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Furthermore, the synovial fluid from rabbits injected with microcrystalline sodium urate significantly decreased (125)I-CCF binding to neutrophils. The binding of (125)I-CCF to its neutrophil receptor was not significantly reduced by the synovial fluid of colchicine-treated rabbits nor by the synovial fluid of control rabbits injected with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Colchicine (10 and 0.1 muM) was shown to have no effect upon the binding of (125)I-CCF to its cell receptor.

Animals

A proposed model for chemotactic deactivation: evidence for microtubule modulation of polymorphonuclear leukocyte chemotaxis.

Incubation of the CFs Gly-His-Glyc or CCF with PMNs in the absence of a gradient, resulted in a dose-dependent depression in chemotactic activity when, after washing, the cells were challenged with the CFs in a Boyden chamber. When the cells were preincubated with either CF and suitable concentrations of colchicine, the inhibition of chemotaxis that either of these agents induced when incubated with the cells alone was abolished. Deactivation reappeared when the optimal ratio between colchicine and CF was altered in either direction. Ultramicroscopic studies showed an increase in centriole-associated microtubules following incubation of cells with CFs. This increase was arrested by prior exposure of the cells to colchicine. Colchicine did not alter the specific binding of CCF to human neutrophils, and lumicolchicine had no effect on either chemotaxis or deactivation. Our data suggest that the control of PMN chemotaxis is predicted upon microtubule assembly evoked by cell interaction with a chemotactic gradient. Chemotaxis would be prevented by conditions that inappropriately organize responsive microtubules in either a polymerized or depolymerized configuration.

Chemotaxis

Dissociation of the neutrophill functions of exocytosis and chemotaxis.

The peptide Gly-His-Gly is shown to be chemotactic for human neutrophils in vitro and for rabbit neutrophils in vivo but to be unable to induce lysosomal enzyme release from human neutrophils at sublytic concentrations. The failure of this chemotactic peptide to elicit lysosomal enzyme release provides evidence that interactions with a chemotactic receptor does not necessarily activate chemotaxis and exocytosis in the human neutrophil, thus suggesting that the presumed common pathway of exocytosis and chemotaxis may be divergent at the cell receptor and/or postreceptor level.

Albumins

A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis.

The acute inflammatory response to calcium pyrophosphate dihydrate crystals follows the meeting of neutrophils and crystals. The ensuing phagocytosis leads to the generation of a glycoprotein chemotactically active for neutrophils and to the release of lysosomal enzymes. Indomethacin and phenylbutazone, at therapeutic concentrations, impaired phagocytosis of the crystals and generation of chemotactic factor activity. Colchicine had no effect upon phagocytosis but significantly impaired the appearance of chemotactic factor activity.

Arthritis

Induction of arthritis by purified cell-derived chemotactic factor: role of chemotaxis and vascular permeability.

The injection of monosidium urate-induced chemotactic factor into the joint cavities of rabbits induces an acute inflammatory response that resembles the one produced by monosodium urate crystals. The leukocyte accumulation induced by the factor was not accompanied by a measurable increase in vascular permeability as measured by appearance of 125I-albumin in the joint cavity. When histamine was injected into the joints, a marked increase in vascular permeability but no leukocytosis above control levels was observed. The above results suggest that the cell-derived factor is primarily responsible for the accumulation of cells seen in the acute inflammation induced by monosodium urate crystals.

Animals

Calcium pyrophosphate dihydrate (CPPD) crystal-induced chemotactic factor: subcellular localization, role of protein synthesis and phagocytosis.

A factor with chemotactic properties for polymorphonuclear leukocytes appears in their lysosomal fraction following phagocytosis of CCPD crystals. The factor, whose appearance was blocked by inhibition of protein synthesis, was estimated to have a molecular weight of 8,400 daltons. Inhibition of crystal phagocytosis by cytochalasin B was also shown to inhibit the generation of chemotactic factor activity, indicating that ingestion of the crystals by the cell is essential for the generation of the CPPD crystal-induced chemotactic factor. This latter finding provides a clue in the understanding of the development and termination of the acute pseudogout attack.

Calcium Pyrophosphate

Urate crystal-induced chemotactic factor: isolation and partial characterization.

A factor with chemotactic properties for neutrophils and mononuclear cells was extracted from the lysosomal fraction of both human and rabbit neutrophils that had been allowed to phagocytose monosodium urate crystals. The chemotactic factor was found to be a glycoprotein with a mol wt of 8,400 daltons. The factor is heat labile and has chemotactic activity for human as well as rabbit cells. Preincubation of the cells with the urate induced chemotactic factor or with complement activated plasma prevents the cell from migrating chemotactically when challenged with either factor in the chemotactic chamber. The chemotactic factor induces release of lysosomal enzymes for cytochalasin B treated human neutrophils.

Glucuronidase

Fluorimetric method for the detection of anti-DNA antibodies in serum.

A method for the detection of native anti-DNA antibodies in serum is described. The method is based on the reactivity of fluorescein isothiocyanate with DNA, forming a complex capable of combining with anti-DNA antibodies. The fluorescein content of the precipitated fluorescein-DNA anti-DNA complex is then measured in a fluorometer. The assay is accurate, highly reproducible, and inexpensive to perform. Comparative studies performed with the Farr assay show the fluorimetric method to be more sensitive in detecting anti-DNA antibodies in the serum of SLE patients.

Antibodies, Antinuclear