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Biomedical subjects

C Edelstein

Publications and source records attributed to C Edelstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Transpupillary thermotherapy for choroidal melanoma: tumor control and visual results in 100 consecutive cases.

OBJECTIVE: The authors evaluated the results of primary transpupillary thermotherapy for choroidal melanoma in 100 cases. DESIGN: Prospective nonrandomized analysis of treatment method. PARTICIPANTS: One hundred patients with choroidal melanoma were studied. MAIN OUTCOME MEASURES: Tumor response, ocular side effects, and visual results. RESULTS: Of 100 consecutive patients with choroidal melanoma treated with transpupillary thermotherapy, the mean tumor basal diameter was 7.1 mm and tumor thickness was 2.8 mm. The tumor margin touched the optic disc in 34 eyes (34%) and was beneath the fovea in 42 eyes (42%). Documented growth was present in 64 eyes (64%), and known clinical risks for growth were present in all of the remaining 36 eyes (36%), with an average of 4 of 5 statistical risk factors for growth per tumor. After a mean of three treatment sessions and 14 months of follow-up, the mean tumor thickness was reduced to 1.4 mm. Treatment was successful in 94 eyes (94%) and failed in 6 eyes (6%). Three patients with amelanotic tumors showed no initial response to thermotherapy, but subsequent intravenous indocyanine green administration during thermotherapy resulted in improved heat absorption and tumor regression to a flat scar. The six eyes classified as treatment failures included four eyes with tumors that showed partial or no response to thermotherapy, thus requiring plaque radiotherapy or enucleation, and two eyes with recurrence, subsequently controlled with additional thermotherapy. After treatment, the visual acuity was the same (within 1 line) or better than the pretreatment visual acuity in 58 eyes (58%) and worse in 42 eyes (42%). The main reasons for poorer vision included treatment through the foveola for subfoveal tumor (25 eyes), retinal traction (10 eyes), retinal vascular obstruction (5 eyes), optic disc edema (1 eye), and unrelated ocular ischemia (1 eye). Temporal location (versus nasal and superior, P = 0.02) and greater distance from the optic disc (P = 0.04) were risks for retinal traction. CONCLUSIONS: Transpupillary thermotherapy may be an effective treatment for small posterior choroidal melanoma, especially those near the optic disc and fovea. Despite satisfactory local tumor control, ocular side effects can result in decreased vision. Longer follow-up will be necessary to assess the impact of thermotherapy on ultimate local tumor control and metastatic disease.

Adult↗
PubMed1998

Oculoplastic experience with the cosmetic use of botulinum A exotoxin.

BACKGROUND: Botulinum toxin is a neuromuscular blocking agent produced by the bacterium Clostridium botulinum. It has been used as a therapeutic agent in ophthalmology for over 18 years. OBJECTIVE: To present the cosmetic use of botulinum toxin in oculoplastic surgery. METHODS: We present our experience with botulinum toxin as a cosmetic agent. RESULTS: Botulinum toxin was successful in treating hyperfunctional lines of the face and neck. CONCLUSIONS: Botulinum toxin is a safe and effective method of treating dynamic lines of the face and neck.

Botulinum Toxins, Type A↗
PubMed1998

Fat repositioning in lower eyelid blepharoplasty.

Cosmetic lower eyelid surgery is not about removing excess skin, muscle, and fat. Rather, it is about restoring eyelid/midface contour. By the third decade of life, the suborbital orbicularis oculi fat begins to descend and the orbital septum weakens and bows forward creating the classic "double convexity deformity." The removal of eyelid fat simply converts this deformity to a "concavity/convexity deformity." The lower eyelid fat redistribution procedure, as described herein, can be used to address this problem.

Adipose Tissue↗
PubMed1998

The transeyelid subperiosteal midface-lift in the unhappy postblepharoplasty patient.

The unhappy postblepharoplasty patient with lateral canthal dystopia, round eye, and scleral show presents perhaps the single greatest challenge to the aesthetic reconstructive surgeon. The problem may be as simple as a lax eyelid, which is inferiorly displaced by gravity or as complex as an eyelid, which has full thickness vertical inadequacy in each of the three eyelid lamellae. The transeyelid subperiosteal midface-lift with lower eyelid reconstruction is a reliable procedure for addressing full thickness lower eyelid vertical tissue inadequacy by totally reconstructing the lower eyelid by the classic three individual layer reconstructive technique. Vertical and horizontal adequacy or inadequacy for each of the three eyelid layers is determined and then individually addressed in the total eyelid reconstruction. This procedure has the potential to fully reconstruct and reposition the lower eyelid and lateral canthus such that the final position, function, and appearance is as good or better than it was before the changes caused by time, gravity, and previous surgery.

Blepharoplasty↗
PubMed1997

Polymorphonuclear cells isolated from human peripheral blood cleave lipoprotein(a) and apolipoprotein(a) at multiple interkringle sites via the enzyme elastase. Generation of mini-Lp(a) particles and apo(a) fragments.

Incubation of polymorphonuclear cells (PMN), isolated from human peripheral blood, with either lipoprotein(a) (Lp(a)) or free apolipoprotein(a) (apo(a)), derived from the parent Lp(a), caused in both cases a multisite fragmentation of apo(a) inhibited by methoxysuccinyl-Ala-Ala-Pro-Val-CH2Cl, a specific elastase inhibitor. The major cut site was at the interkringle region between apo(a) kringles IV-4 and IV-5 (Ile3520-Leu3521). The other cleavages were between kringles IV-7 and IV-8 (Thr3846-Leu3847) and between kringles IV-10 and V (Ile4196-Gln4197). The elastase-induced fragmentation of apo(a) was the same whether free or as a member of Lp(a), indicating that the disulfide bond between apo(a) and the apoB100 component of Lp(a) did not hinder the elastase action. Lp(a) fragments containing kringle IV-9 retained the linkage to apoB100 via the disulfide bond, forming mini-Lp(a) particles in which the size of apo(a) varied according to the size of the fragments produced by the elastase digestion. The proteolytic fragmentation was unaffected by apo(a) size polymorphism within the range examined. PMN elastase also caused a partial proteolysis of apoB100 whether as a component of Lp(a), Lp(a) freed of apo(a), or authentic low density lipoprotein without an apparent destabilization of these lipoprotein particles. Proteolysis of Lp(a) by PMN was due to an elastase activity that was 3.5% of that observed when PMN were activated by N-formyl-Met-Leu-Phe. A portion of the released elastase was found to be associated in an active form with both Lp(a) and low density lipoprotein even in an ultracentrifugal field at high salt concentrations. Taken together, our results indicate that apo(a) undergoes important proteolytic modifications by PMN elastase, which exhibits specificity for peptide bonds located in the interkringle domains of apo(a). In the case of Lp(a), elastase cleavage causes the formation of mini-Lp(a) particles with a protein moiety containing a truncated apo(a). Elastase-mediated proteolytic events may occur in vivo under conditions associated with either an excessive leakage of elastase from PMN and/or deficiencies of natural inhibitors of this enzyme.

Amino Acid Chloromethyl Ketones↗
PubMed1997

Non-African Burkitt lymphoma presenting with oral thrush and an orbital mass in a child.

PURPOSE: To report an unusual case of orbital involvement with non-African Burkitt lymphoma in a child. METHODS: A 26-month-old boy developed oral thrush and painless right proptosis with eyelid swelling. Magnetic resonance imaging disclosed a diffuse mass involving the inferior, lateral, and superior right orbit and both maxillary sinuses. Incisional biopsy of the orbital mass was performed. RESULTS: Histopathology disclosed diffuse infiltration of the orbital tissues by a high-grade lymphoid neoplasm that showed positive immunoreactivity for B-cell markers. Immunoglobulin gene rearrangement studies disclosed a characteristic t(8;14) translocation consistent with a small, noncleaved malignant lymphoma of the Burkitt type. CONCLUSION: Non-African Burkitt lymphoma may manifest with orbital involvement.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Complications of motility peg placement for the hydroxyapatite orbital implant.

PURPOSE: The hydroxyapatite implant is an ocular motility implant designed to provide natural movement of the artificial eye. The movement of the prosthesis is maximized when the implant is coupled to the prosthesis via a peg. The purpose of this study is to determine the complications of the hydroxyapatite motility peg and the factors related to those complications. DESIGN: Retrospective review of 47 cases over 5 years. METHODS: A retrospective review was performed on all cases of hydroxyapatite motility peg placement. The technique of hydroxyapatite and peg placement, follow-up details, and complications of the peg were recorded. RESULTS: The complications of peg placement included peg extrusion in 26% (12 of 47), nonspecific conjunctivitis in 6% (3 of 47), audible click in 6% (3 of 47), temporary excessive conjunctival edema in 4% (2 of 47), and temporary excessive postoperative pain in 4% (2 of 47). There were no cases of infection, persistent pain, persistent edema, or discharge at peg site. The median time interval from peg placement to extrusion was 16 months (range, 1-52 months). The only statistically significant factor related to peg extrusion was age over 50 years (P = 0.04). There was a trend toward peg extrusion with use of a nonsleeved peg (versus sleeved peg) (P = 0.10). The extrusion rate was 32% (12 of 38) for nonsleeved pegs and 0% (0 of 9) for sleeved pegs. Factors unrelated to peg extrusion were patient sex, prior ocular surgery or radiotherapy, presence of giant papillary conjunctivitis, time interval from enucleation to peg placement, and degree of implant vascularization on magnetic resonance imaging. Of the 12 nonsleeved pegs that extruded, a sleeved peg system was subsequently successfully placed in 5 patients, a nonsleeved peg in 1 patient, and 6 patients remained without a peg system. CONCLUSIONS: Hydroxyapatite motility pegs have relatively few complications except for extrusion. The rate of extrusion can be minimized by employing a sleeved peg rather than a nonsleeved peg system.

Adolescent↗
PubMed1997

Lipoprotein(a): identification of subjects with a superbinding capacity for fibrinogen.

We have previously shown that the binding of lipoprotein(a) [Lp(a)] to immobilized fibrinogen involves the domain located in kringles IV-5 to IV-8, but not kringle IV-10. In extending those studies to subjects living in Chicago and in the island of Sardinia, we found that about 6% of them had an Lp(a) with Bmax values of 27.7+/-6.0 fmol, which were about 5-8-fold higher than those of controls (3.4+/-2.8 fmol) and in the range of those observed for free apo(a) derived from the Lp(a) of controls (36.6+/-2.9 fmol). This superbinding phenotype was unaffected by age, sex, type of lipid disorder and hypolipidemic agents, and also had a familial incidence. We are currently exploring the hypothesis that this fibrinogen superbinding phenotype is due to conformational changes of apolipoprotein(a) [apo(a)] resulting from the lipid content and composition of the Lp(a) particle and/or sequence anomalies in the kringle domain IV-5 to IV-8.

Age Factors↗
PubMed1997

Learning about the structure and biology of human lipoprotein [a] through dissection by enzymes of the elastase family: facts and speculations.

Lipoprotein[a], Lp[a], represents a class of lipoprotein particles that have as a protein moiety apoB-100 linked by a disulfide bridge to a multi-kringle structure, apolipoprotein[a], or apo[a]. It is now possible to separate from Lp[a] a free apo[a] able to reassociate with apoB-100-containing lipoproteins to restore the parent lipoprotein complex. Apo[a], whether free or a constitutive component of Lp[a], can be cleaved at interkringle sites by the action of enzymes of the elastase family generating fragments that differ in structural, functional, and metabolic properties. In the case of Lp[a], elastase digestion generates a miniLp[a] particle, which contains the apo[a] COOH-terminal domain able to bind to lysine, fibrinogen, fibronectin, and proteoglycans. This domain may also be generated by elastase type enzymes secreted by activated macrophages and smooth muscle cells in the arterial intima as a part of the chronic inflammation that characterizes the atherosclerotic process. Thus, the apo[a] immunoreactive material, which has been described in the atherosclerotic plaque, may represent miniLp[a] and/or apo[a] fragments accumulating in the vessel wall as a function of their relative affinity for the components of the extracellular matrix and producing complexes with an atherothrombogenic potential. This potential may depend on several factors: kringle folding and conformation, susceptibility of the linkers to proteolytic cleavage, binding specificity of given apo[a] fragments to the matrix components of the arterial intima, and the overall inflammatory status of the arterial wall.

Amino Acid Sequence↗
PubMed1996

Evidence that the fibrinogen binding domain of Apo(a) is outside the lysine binding site of kringle IV-10: a study involving naturally occurring lysine binding defective lipoprotein(a) phenotypes.

It is now established that the lysine binding site (LBS) of apo(a) kringle IV-10, and particularly Trp72, plays a dominant role in the binding of lipoprotein(a) [Lp(a)] to lysine. To determine the role of the LBS in the binding of Lp(a) to fibrinogen, we examined the binding to plasmin-modified (PM) fibrinogen of human and rhesus monkey Lp(a) species classified as either Lys' or Lys- based on their capacity to bind lysine Sepharose and to have Trp or Arg, respectively, in position 72 of the LBS of kringle IV-10. We also examined the free apo(a)s obtained by subjecting their corresponding parent Lp(a)s to a mild reductive procedure developed in our laboratory. Our results show that both Lyst and Lys- Lp(a)s and their derived apo(a)s, bound to PM-fibrinogen with similar affinities (Kds: 33-100 nM), whereas the B(max) values were threefold higher for apo(a)s. Both the lysine analog epsilon-aminocaproic acid and L-proline inhibited the binding of Lp(a) and apo(a) to PM fibrinogen. We conclude that the LBS of kringle IV-10 is not involved in this process and that apo(a) binds to PM-fibrinogen via a lysine-proline-sensitive domain located outside the LBS and largely masked by the interaction of apo(a) with apoB100. The significant difference in the PM fibrinogen binding capacity also suggests that apo(a) may have a comparatively higher athero-thrombogenic potential than parent Lp(a).

Adult↗
PubMed1996

Functional and metabolic differences between elastase-generated fragments of human lipoprotein[a] and apolipoprotein[a].

We have previously shown that a functional free apolipoprotein[a] (apo[a]) can be isolated from its parent lipoprotein[a] (Lp[a]) by a mild reductive procedure. To shed further light on the properties of Lp[a] and apo[a] we subjected them to a limited proteolysis by porcine pancreatic elastase. This enzyme cleaved both at the Ile3520-Leu3521 bond in the linker between kringles IV-4 and IV-5 of apo[a] generating two fragments F1 and F2. In contrast to F1, which represented the N-terminal portion of apo[a] and was functionally inert, F2, representing the C-terminal domain, bound to lysine-Sepharose, fibrinogen, and fibronectin and formed a miniLp[a] particle when incubated with LDL. The proteolytic pattern by pancreatic elastase was also exhibited by human leukocyte elastase. F1, injected intravenously into normal mice, was rapidly cleared (Ty2, 2.9 h) and after 1 h fragments in the size range of 100-33 kDa were observed in the urine. In turn, F2 had a longer residence time (Ty2, 5 h) and was excreted in the urine only after 5 h as fragments of 70-45 kDa. Fragments in the same size range as found after F1 injection were also present in the urine after injection of apo[a] or Lp[a]. Moreover, apo[a] fragments of the size seen in mouse urine were spontaneously present in normal human urine and appeared derived from larger apo[a] fragments in the plasma. Our results indicate that enzymes of the elastase family cleave human apo[a] in vitro into two main fragments that differ in structural and functional properties and metabolic behavior. The comparable size of apo[a] fragments observed in the urine of humans and injected mice invites the speculation that enzymes of the elastase family may play a role in the biology of Lp[a] in vivo.

Amino Acid Sequence↗
PubMed1995

Determinants of lipoprotein(a) assembly: a study of wild-type and mutant apolipoprotein(a) phenotypes isolated from human and rhesus monkey lipoprotein(a) under mild reductive conditions.

We previously observed that rhesus monkey lipoprotein(a) [Lp(a)], is lysine-binding defective (Lys-) and attributed this deficiency to the presence of Arg72 in the lysine-binding site (LBS) of kringle IV-10 of apolipoprotein(a) [apo(a)] [Scanu, A.M., Miles, L.A., Fless, G.M., Pfaffinger, D., Eisenbart, J., Jackson, E., Hoover-Plow, J.L., Brunck, T., & Plow, E.F. (1993) J. Clin. Invest. 91, 283-291]. We also identified human mutants having Arg72 instead of Trp72 (wild type) in the LBS of kringle IV-10 [Scanu, A M., Pfaffinger, D., lEE, J.C., & Hinman, J. (1994) Biochim. Biophys. Acta 1227, 41-45]. Unique to the human mutant phenotype were the very low levels of plasma Lp(a), suggesting structural differences between human and rhesus apo(a) and a possible divergent mode of Lp(a) assembly. In order to explore the possibility of a relationship between apo(a) LBS and Lp(a) assembly, we developed a novel method for isolating wild-type and mutant apo(a) phenotypes in a free form by subjecting each parent Lp(a) to mild reductive conditions using 2 mM dithioerythritol (DTE) and 100 mM of the lysine analogue, epsilon-aminocaproic acid (EACA). The application of this method to the study of wild-type and mutant apo(a) species showed that regardless of the source of Lp(a), i.e., positive lysine binding (Lys+) or negative lysine binding (Lys-), all of the isolated free apo(a)s were Lys+. Moreover, incubation of free apo(a)s with their autologous human or rhesus low-density lipoproteins (LDL) generated Lp(a) complexes which were structurally and functionally indistinguishable from their parent native Lp(a). In each instance, the reassembly process was inhibited by the presence of either EACA or proline. These two reagents had a minimal effect on either Lp(a) or reassembled Lp(a) [RLp(a)]. Free apo(a) bound to apoB100 of very low density lipoproteins (VLDL) to form a triglyceride-rich Lp(a). These results show that (1) both human and rhesus Lp(a) are amenable to dissassembly and reassembly, (2) the presence of Arg72 in the LBS of kringle IV-10 is not involved, at least directly, in this process, (3) its cleavage from apoB100 opens up in apo(a) a domain that is both EACA and proline sensitive and involved in Lp(a) assembly, and (4) the apoB100 of VLDL is also competent to bind apo(a). Our observations also suggest that the difference in plasma Lp(a) levels between the rhesus and the human mutant, both having Arg72 in the LBS of apo(a) kringle IV-10, is not related to the assembly process, but more likely to a divergence in production/secretion rates between the two apo(a) phenotypes.

Aminocaproates↗
PubMed1994

Oleate stimulates the formation of triglyceride-rich particles containing apoB100-apo(a) in long-term primary cultures of human hepatocytes.

Hepatocytes prepared from normal human liver donors were maintained in a synthetic, nutritionally defined, serum-free medium for up to 60 days with continuous secretion of the major plasma lipoproteins. By Western blot analysis, both cell lysates and culture media contained apo(a), both unbound and bound to apo B100, in varying proportions, dependent on the liver donor. In the medium of cells pulse-labeled for 16 h with [35S]methionine the apo(a)-apoB100 complex was predominantly found in the d < 1.006 g/ml triglyceride-rich particles (TRP). Incubation of the cells with a bovine serum albumin-potassium oleate complex in a molar ratio of 1:4 caused a twofold to threefold increase of the TRP-containing apoB100-apo(a). In the 48 h unlabeled conditioned medium apoB100-apo(a) was distributed among the d < 1.006, d < 1.063 and d < 1.21 g/ml lipoproteins, with a small amount in the d > 1.21 g/ml sedimenting fraction, suggesting that the newly secreted apoB100-apo(a)-containing TRP had undergone remodeling. The results indicate that primary human hepatocyte cultures produce both apo(a) and apoB100-apo(a) and that the latter affiliates preferentially with TRP, forming a lipoprotein complex that is affected by endogenous triglyceride synthesis, and can be metabolically modified in the culture medium of human primary hepatocytes.

Apolipoprotein B-100↗
PubMed1994

Post-prandial Lp(a): identification of a triglyceride-rich particle containing apo E.

A VLDL-like particle containing the apo B100-apo(a) complex was isolated from the post-prandial plasma of subjects fed a fat meal enriched in saturated fatty acids. The abundance of this lipoprotein particle, that we call TG-Lp(a), varied among subjects but not in the same subject. TG-Lp(a), but not the classic Lp(a), contained apo E; this apolipoprotein may cause divergence in cellular uptake and degradation between these two classes of lipoproteins.

Apolipoprotein B-100↗
PubMed1994

Apolipoprotein(a): structural and functional consequences of mutations in kringle type 10 (or kringle 4-37).

The size polymorphism of Lp(a) is well recognized. It is now apparent that there is an additional polymorphism resulting from mutations occurring at the kringle level. One of these mutations involves a trp72 to arg substitution in apo(a) kringle type 10 and is attended by a defective binding of Lp(a) to immobilized lysine/fibrin. Other mutations affecting the other amino acids of the "lysine-binding pocket" may have similar functional consequences and may be important at the clinical level in terms of thrombogenesis.

Amino Acid Sequence↗
PubMed1993

Hypoalphalipoproteinemia: postprandial response of subjects with preprandial normotriglyceridemia and hypertriglyceridemia to various diets.

The effect of a single oral fat meal (60 g fat/m2 body surface area) enriched in either saturated (SFA) or polyunsaturated ([PUFA] omega-6 or omega-3) fatty acids on postprandial lipoprotein levels was studied in four men with primary hypoalphalipoproteinemia (HP) and in four age- and sex-matched controls. Vitamin A was included in the meal to label intestinally derived triglyceride-rich particles (TRP) with retinyl palmitate (RP). The HP subjects were either mildly hypertriglyceridemic (group A) or normotriglyceridemic (group B) and were phenotyped for post-heparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and apolipoprotein (apo) E isoforms. Postprandial total plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and RP and TG concentrations in the chylomicron (Sf > 1,000) and nonchylomicron (Sf > 1,000) fractions were evaluated for 24 hours after the meal. At each time point, HDL composition and size and apolipoprotein distributions were also measured. Following the SFA meal, HP subjects had maximal plasma TG levels at 8 hours (4 hours in controls) with a slow return to baseline levels at 12 to 24 hours (8 to 12 hours for controls). In contrast, after the omega-6 meal plasma TG levels decreased in group A subjects, while group B subjects and controls showed only a small increase. The results after the omega-6 meal were intermediate between the SFA and the omega-3 meal. When compared with group B, subjects in group A showed higher levels of RP-associated TRP, slower clearance rates, 30% to 50% lower fasting LPL activity, and 1.5-fold to twofold higher fasting plasma apo C-III levels. The major preprandial HDL subclass in HP subjects was HDL3, which showed a relative decrease in cholesterol esters (CE) and an increase in TG levels following the SFA meal. After the omega-3 meal, HDL of group A subjects showed a decrease in TG, a reciprocal increase in CE, and either no changes or minor changes in phospholipid (PL) and free-cholesterol (FC) levels. The results show that HP subjects with mild preprandial hypertriglyceridemia respond to a single fat meal differently than subjects with normotriglyceridemia, and that this difference is the result of HP in addition to other factors such as low LPL and HTGL activities, high plasma apo C-III levels, and apo E2 phenotype.

Adult↗
PubMed1993

Research cost analyses to aid in decision making in the conduct of a large prevention trial, CARET. Carotene and Retinol Efficacy Trial.

Because of their larger study populations and longer durations, prevention trials typically are more costly than treatment trials. Thus it is important to analyze costs systematically to aid in making cost-effective decisions during the conduct of prevention trials as well as in the original design. Cost analysis must be tied to sample size estimation because costs depend on such factors as the total number of person-years of follow-up and the number of trial outcomes, which are not basic design parameters but are derived quantities resulting from sample size estimation. We illustrate the use of cost analysis to decide among options for future conduct of an ongoing prevention trial with three issues that have arisen during the Carotene and Retinol Efficacy Trial (CARET): the trade-off between extending the duration of the trial or increasing the number of participants, the effect on costs of delay in accrual, and the cost effectiveness of particular retention activities.

Anticarcinogenic Agents↗