Search PubMed⌕ Search

Biomedical subjects

D M Schwartz

Publications and source records attributed to D M Schwartz.

At least 19 recordsLinked to original sources
PubMed1999

Human trabecular meshwork cells as a thyroid hormone target tissue: presence of functional thyroid hormone receptors.

PURPOSE: To determine whether human trabecular meshwork cells (HTM) are a potential target tissue for thyroid hormone (3,3',5-triiodothyronine, T3). METHODS: Cultured HTM were assayed for the presence of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) by reverse-transcriptase polymerase chain reaction (RT-PCR) to detected TR and RXR mRNA, and by immunohistochemistry to detect nuclear TR and RXR proteins. Functionality of the TR was determined by analysis of 125I-T3 binding affinity and capacity in HTM nuclear extracts. Effects of T3 on modulation of hyaluronic acid (HA) levels in HTM were measured as a function of dose and duration of T3 administration. RESULTS: Analysis of RT-PCR and immunohistochemistry demonstrated that cultured HTM expressed TRalpha1, TRalpha2, and TRbeta1 but not TRbeta2; and RXRalpha but not RXRbeta and RXRgamma isoforms. Saturation binding and analysis of 125I-T3 to HTM nuclear extracts revealed Kd of 57 pM. The number of T3 binding sites extrapolated from a Scatchard plot was 7.3 x 10(10)/microg of HTM nuclear protein extract. T3 supplementation reduced the concentration of HA in the cell medium by 32-43% compared to cells grown in the absence of T3. CONCLUSIONS: Cultured HTM express three TR isoforms and one RXR isoform, bind T3 with an affinity similar to that of TR in responsive cells, and modulate their HA production in response to T3. These findings indicate that the human trabecular meshwork tissue has the capacity to respond to thyroid hormones.

Adult↗
PubMed1999

Visual and anatomic outcomes associated with posterior segment complications after ganciclovir implant procedures in patients with AIDS and cytomegalovirus retinitis.

PURPOSE: To determine anatomic and visual acuity outcomes of posterior segment complications after ganciclovir implant surgery. METHODS: We reviewed the medical records of 63 patients with acquired immunodeficiency syndrome who had active cytomegalovirus retinitis in 82 eyes and who underwent 110 consecutive ganciclovir implant procedures. Preoperative and postoperative visual acuity, type of postoperative complication, treatment, and lines of visual acuity change were determined. RESULTS: Thirty-eight eyes of 19 patients had bilateral ganciclovir implant procedures, and 25 eyes of 19 patients underwent two or more ganciclovir implant procedures. Thirteen (12%) of 110 ganciclovir implant procedures developed posterior segment complications: rhegmatogenous retinal detachment in six, vitreous hemorrhage in four, endophthalmitis in two, and cystoid macular edema with epiretinal membrane in one. Treatment included pars plana vitrectomy with silicone oil in two cases and without silicone oil in three cases, scleral buckling in one, intravitreal antibiotic injection in two, and laser photocoagulation in two. Overall, median visual acuity was 20/25 preoperatively. Median follow-up was 6 months for all eyes and 7 months for eyes with complications. Postoperative median visual acuity was 20/25 for eyes without complications vs 20/40 at 1 month, 20/60 at 3 and 6 months, and 20/100 at 12 months in eyes with complications (P < .001). More eyes with than without complications lost 2 or more lines of visual acuity (P < .001). CONCLUSION: Postoperative complications occurred in 12% of the ganciclovir implant procedures and were associated with decreased visual acuity despite treatment.

AIDS-Related Opportunistic Infections↗
PubMed1998

Tetrodotoxin: anesthetic activity in the de-epithelialized cornea.

BACKGROUND: Tetrodotoxin (TTX) binds with high affinity to sodium channels and produces local anesthesia. We investigated whether TTX is an effective, long-acting corneal anesthetic in rabbits. METHODS: After mechanical debridement of the central corneal epithelium, topical TTX (1 mM, 0.1 mM, or 0.01 mM) was applied to one eye each of 18 New Zealand White rabbits. The fellow eye of each rabbit was treated with control vehicle. Blink response to a mechanical stimulus was assessed. Blink response was also assessed every 3 h for 30 h in 6 rabbits treated with 1 mM TTX administered every 6 h. In a separate group of 12 rabbits with central epithelial debridement, the rate of epithelial healing was compared between animals treated with topical 1.0 mM TTX and animals receiving no treatment. RESULTS: After 4 h, eyes treated with 1.0 mM and 0.1 mM TTX were anesthetic. At 6 h, five of six rabbit eyes treated with 1.0 mM TTX were still partially anesthetic. By 8 h, the mean anesthesia score for 1.0 mM TTX was approaching normal. With multiple dosing, all six rabbit eyes remained anesthetic for the duration of the experiment. There was no significant difference in the rate of re-epithelialization between eyes treated with TTX and untreated controls. There was no evidence of systemic or local toxicity from topical TTX. CONCLUSION: In a rabbit model, TTX is a long-acting topical anesthetic that retains its effectiveness when administered repeatedly over 24 h and does not inhibit epithelial healing. It may have application in management of pain after photorefractive keratectomy.

Administration, Topical↗
PubMed1998

Experimental study of tetrodotoxin, a long-acting topical anesthetic.

PURPOSE: To determine the effectiveness and toxicity of tetrodotoxin for use as a long-acting topical anesthetic. METHODS: Four groups of six rabbits each received a 40-microl aliquot of either tetrodotoxin in one of three concentrations (10 mM, 1 mM, or 0.1 mM) or proparacaine 0.5% into the inferior conjunctival cul-de-sac of one eye, with the fellow eye of each rabbit receiving 40 microl of a 60-mM, pH 4.3 sodium citrate vehicle as a control. Corneal sensation was tested for up to 8 hours after administration of drugs, and response was noted by no blink, partial blink without full eyelid closure, and full blink. Slit-lamp examination at 12 and 24 hours after administration and pachymetry before and 24 hours after administration were performed to detect corneal toxicity. RESULTS: Rabbits receiving all three concentrations of tetrodotoxin did not demonstrate any ocular irritation, corneal thickening, or signs of systemic toxicity. At a dose of 10 mM, tetrodotoxin produced an anesthetic effect lasting up to 8 hours. At 1 mM, tetrodotoxin was an effective but shorter-acting anesthetic. At 0.1 mM, tetrodotoxin had no significant anesthetic effect. Proparacaine-treated rabbits initially were anesthetic, but this effect was largely gone by 1 hour and completely gone by 3 hours. CONCLUSIONS: Tetrodotoxin is a long-acting topical anesthetic in the rabbit cornea. Although additional toxicity studies are required, tetrodotoxin may provide an effective, long-lasting topical anesthetic for use in pain control after corneal procedures such as photorefractive keratectomy.

Anesthesia, Local↗
PubMed1998

Experimental use of tetrodotoxin for corneal pain after excimer laser keratectomy.

PURPOSE: To determine the duration of anesthesia, effect on corneal reepithelialization, and systemic toxicity of topical tetrodotoxin (TTX) administered after excimer laser keratectomy. METHODS: Two groups of six rabbits each underwent excimer laser keratectomy in the right eye to create a 5-mm-diameter wound, 75 mm in depth. One group then received a 40-microl aliquot of topical 1 mM TTX into the injured eye, whereas the other group received 40 microl of the sodium citrate vehicle as a control. The rabbits were treated with TTX or vehicle again at 6, 12, 18, and 24 h. Corneal sensation was tested at 3, 6, 9, 12, 15, 18, 21, 24, 30, 32, and 40 h. To determine whether TTX inhibited corneal reepithelialization, compared with vehicle-treated control eyes, the healing rate of the epithelial defect was measured. RESULTS: Administration of TTX every 6 h for 24 h produced nearly complete anesthesia for > or = 30 h. At 32 h, 8 h after the final application of TTX, there was still significant anesthesia of the TTX-treated corneas (p = 0.0325, Wilcoxon test). Normal corneal sensation in all TTX-treated animals returned at 40 h, or 16 h after the final dose. In contrast, vehicle-treated eyes all had normal sensation for nearly the entire duration of the experiment. At 40 h, the TTX-treated eyes had slightly larger defects than vehicle-treated eyes, 7.85+/-1.74 versus 4.54+/-1.31 mm2 (p < 0.025, t test). However, at 49 h and thereafter, both groups were equally healed (p > 0.05, t test). No systemic toxicity was observed in any of the rabbits. CONCLUSION: Topical TTX is a long-acting and nontoxic local anesthetic in a rabbit model of excimer laser keratectomy.

Anesthesia, Local↗
PubMed1998

Expression of CD44 isoforms in cultured human trabecular meshwork cells.

PURPOSE: To determine the expression of CD44 isoforms in cultured human trabecular meshwork (HTM) and to discuss their possible relationship with outflow facility. METHODS: CD44 isoform expression in cultured HTM was qualitatively examined using immunohistochemistry and RT-PCR analysis. RESULTS: Immunohistochemistry of cultured HTM showed intense staining with a CD44s antibody, and with antibodies against CD44 exon 7, exon 11-12 and exon 14. By RT-PCR, at least three isoforms of CD44 were expressed in HTM: CD44s, CD44v-III and CD44v-I. CONCLUSIONS: At least three isoforms of CD44 are expressed in the HTM. CD44 may play a role in binding and turnover of hyaluronic acid in the trabecular meshwork, thereby regulating outflow facility.

Cells, Cultured↗
PubMed1997

Aqueous hyaluronic acid concentration: comparison in pediatric and adult patients.

PURPOSE: To determine if there is an age-related increase in human aqueous hyaluronic acid (HA) concentration. METHODS: HA concentrations were measured in 102 specimens of human aqueous humour obtained during intraocular surgery. Patient age ranged from one month to 93 years. Measurement of the HA concentration in the specimens was performed by a modified ELISA-like assay using a biotinylated HA-binding peptide. RESULTS: An approximate five-fold increase in the mean aqueous HA concentration was observed between the pediatric (0.33 microgram/ml, n = 5) and the adult patients (1.72 micrograms/ml, n = 97, p < 0.0002). Among the adult patients, however, there was a poor correlation between age and aqueous HA concentration. CONCLUSIONS: Adult aqueous humor has a significantly higher HA concentration than aqueous obtained from pediatric patients. The source of this increase is unclear, but may be from anterior segment production of HA, or alternatively, from anterior diffusion of vitreous HA.

Adult↗
PubMed1997

Hyaluronan polymer size modulates intraocular pressure.

To investigate whether the occasional increase in intraocular pressure that may arise following injection of sodium hyaluronan into the anterior segment during intraocular surgery is related to the polymer size of hyaluronan, controlled fragmentation of hyaluronan chains in vitro was obtained using progressive incubation with testicular hyaluronidase. The profile of molecular sizes of the hyaluronan polymers in various preparations was determined using molecular sieve column chromatography. Individual preparations were injected into six rabbit eyes and intraocular pressures were measured every one-half hour for 12 hours. Longer incubations of hyaluronan with hyaluronidase resulted in more extensive degradation with accumulation of shorter chain lengths. In the rabbit, mean intraocular pressure for 12 hours following intracameral injection of hyaluronic acid (HA) is proportional to the polymer size of HA. The occasional elevation of intraocular pressure that occurs following injection of hyaluronan during ophthalmic surgery can be avoided in part by assuring the rapid fragmentation of the large molecular size hyaluronan polymer.

Animals↗
PubMed1997

Depiction of pulmonary emboli with spiral CT: optimization of display window settings in a porcine model.

PURPOSE: To determine optimal spiral computed tomographic (CT) image display for depiction of pulmonary emboli (PE). MATERIALS AND METHODS: Autologous PE detected in 10 pigs with contrast material-enhanced spiral CT were displayed with six display window settings (standard mediastinal window and five modified windows referenced to attenuation values in pulmonary artery [PA] branches). The thrombus gray level and gray level contrast and separability of PE versus those of the local PA branch were computed for each window setting; results were compared with repeated measured analysis of variance. RESULTS: Of 114 PE detected pathologically, 28 were visible with spiral CT. Two of the 28 PE were not detectable with standard mediastinal windows. Statistically significantly improved gray level contrast and separability were noted with modified windows referenced to the second-order PA branch and the local PA branch than with the standard mediastinal and other modified window settings (P < .05). However, thrombus gray level was statistically significantly higher with the standard mediastinal window (P < .05). CONCLUSION: PE are best depicted as filling defects when displayed with a modified window referenced to the right or left main PA attenuation. Standard mediastinal windows are useful for identifying vessels that are occluded completely with PE.

Acute Disease↗
PubMed1997

Influence of nitrous oxide on posterior tibial nerve cortical somatosensory evoked potentials.

The suppressive effect of the halogenated inhalation anesthesia on cortical somatosensory evoked potentials (cSSEPs) has been well documented. Less studied and appreciated is the effect of nitrous oxide often with a narcotic as an alternative to a potent agent for spinal cord monitoring. This study sought to define more clearly the influence of nitrous oxide on cSSEPs elicited to posterior tibial nerve stimulation. A secondary purpose was to demonstrate the advantage of a total intravenous propofol anesthesia in facilitating uncompromised large-amplitude cSSEPs. Fifty adult patients undergoing anterior cervical discectomy served as the study sample. Brainstem and cortical posterior tibial nerve SSEPs were recorded under two independent anesthesia conditions, namely, nitrous oxide and propofol. Results demonstrated a significant amplitude reduction and latency prolongation with the nitrous oxide versus propofol protocol. cSSEP amplitude with propofol was, on the average, approximately two times larger than that with nitrous oxide. Based on these findings, the use of nitrous-oxide anesthesia is not recommended when limited to monitoring cSSEPs that are already amplitude compromised secondary to existing spinal cord disease.

Adult↗
PubMed1997

Corneal endothelial hyaluronidase: a role in anterior chamber hyaluronic acid catabolism.

The possible role of the human corneal endothelium in the turnover of anterior chamber hyaluronic acid (HA) was investigated. Hyaluronidase, an endoglycosidase that degrades HA and other glycosaminoglycans, is thought to play a role in HA homeostasis. The presence of hyaluronidase in the corneal endothelium was demonstrated immunohistochemically in sections from normal adult human cornea. Additionally, by using a modified enzyme-linked immunosorbent assay-like assay, active hyaluronidase was detected in the supernatant from primary culture human corneal endothelial cells. The optimal activity for the corneal endothelial hyaluronidase was in the acid range (pH 4.0), similar to previously isolated lysosomal hyaluronidase. Further immunohistochemistry showed that the corneal endothelial cells also express CD44, the receptor for HA, which would allow endocytosis of HA. Human corneal endothelial hyaluronidase may play a role in normal anterior segment HA metabolism and in the degradation of highly concentrated HA used as a visco-elastic.

Adult↗
PubMed1996

Guarded microvitreoretinal blade.

During vitreoretinal surgery, the microvitreoretinal blade may be misdirected and injure operating room personnel. A sheated, retractable blade has been developed to reduce the likelihood of such injuries. In the blade's retracted position, a safety feature prevents inadvertent exposure of the sharp blade. This device may have its greatest utility in operating on patients with cytomegalovirus retinitis who require either retinal reattachment surgery or placement of a ganciclovir implant.

Cytomegalovirus Retinitis↗
PubMed1996

Human vitreous hyaluronidase: isolation and characterization.

PURPOSE: Hyaluronic acid (HA) is the predominant glycosaminoglycan (GAG) of the human vitreous. Interaction of this HA with vitreous collagen is important for maintaining gel structure. The mechanism of HA homeostasis in the vitreous is incompletely understood. The aim of this study was to determine whether hyaluronidase, an endoglycosidase that degrades HA, was present in human vitreous. METHODS: Vitreous samples were collected from post-mortem eye bank specimens and from non-hemorrhagic, non-inflamed biopsy specimens. Vitreous hyaluronidase was purified by a series of column chromatographic steps, and its activity was measured by an ELISA-like assay and by substrate gel electrophoresis through and HA-impregnated gel. The purified hyaluronidase was also analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and by Western blotting. RESULTS: Hyaluronidase activity was detected in vitreous samples from both post-mortem and biopsy specimens. The enzyme was most active at acid pH, but demonstrated significant activity at neutral pH. The partially purified enzyme migrated as a 59 kDa protein on SDS-PAGE, and a single band on Western blots. CONCLUSIONS: Hyaluronidase is present in the human vitreous. Thus, hyaluronidase may be involved in HA catabolism in the vitreous and may play a role in determining its gel structure.

Blotting, Western↗
PubMed1996

Efficacy of spinal cord monitoring in scoliosis surgery in patients with cerebral palsy.

Although spinal cord monitoring is recommended during scoliosis surgery, a review from Rancho Los Amigos Medical Center stated that they were only able to obtain reproducible tracings in 53% of cerebral palsy patients. To ascertain that monitoring is both feasible and reliable in these patients, we reviewed the records of 34 consecutive patients with cerebral palsy who had scoliosis surgery at our institution. Spinal cord function was monitored by recording peripheral nerve, cervical/brainstem, and cortical somatosensory evoked potentials to posterior tibial nerve stimulation. Reproducible tracings were achieved in 31 of the 34 patients. Significant intraoperative changes were recorded in 12 of the 31 monitored patients, usually related to and requiring some modifications of the instrumentation. We conclude that with careful technique, spinal cord monitoring using cervical/brainstem somatosensory evoked potentials can be reliably achieved in most patients with cerebral palsy undergoing scoliosis surgery.

Adolescent↗
PubMed1996

Influence of rigid spinal instrumentation on the neurogenic motor evoked potential.

Three case reports are presented to illustrate how placement of spinal instrumentation obliterates previously normal neurogenic motor evoked potentials (NMEPs) elicited by transosseous electrical stimulation. This results in an unacceptably high false-positive rate for NMEP recordings during scoliosis surgery. The loss of the NMEPs was attributed to shunting of electrical current from JO5 spinous process stimulating needles through the metal rod to ground, thus preventing adequate stimulation to the spinal cord. A modification of the transosseous technique with epidural stimulation to improve test reliability is described.

Adolescent↗
PubMed1995

A sensitive and specific polymerase chain reaction-based assay for the diagnosis of cytomegalovirus retinitis.

PURPOSE: To develop a sensitive and specific laboratory assay for the diagnosis of cytomegalovirus retinitis. METHOD: We used a polymerase chain reaction-based assay for detection of cytomegalovirus DNA in vitreous samples. We attempted to detect cytomegalovirus DNA in 19 vitreous samples from patients with the acquired immunodeficiency syndrome (AIDS) who had untreated cytomegalovirus retinitis and in 40 vitreous samples from patients with AIDS who had been treated with systemic ganciclovir or foscarnet, or both. We also attempted to detect cytomegalovirus DNA in vitreous samples from 54 immunocompetent patients, including 32 with retinal detachment or macular hole, 11 with vitreous inflammation, and 11 with vitreous hemorrhage. Additionally, we attempted to detect cytomegalovirus DNA in 15 vitreous samples from patients with AIDS who had vitreoretinal inflammation not caused by cytomegalovirus. RESULTS: Cytomegalovirus DNA was detected in 18 of 19 eyes with untreated cytomegalovirus retinitis. We detected cytomegalovirus DNA in 19 of 40 vitreous samples from patients with previously treated cytomegalovirus retinitis. Cytomegalovirus DNA was not detected in any of 69 patients who did not have a clinical diagnosis of cytomegalovirus retinitis. Thus, the assay had an estimated sensitivity of 95% in detecting untreated cytomegalovirus retinitis and a sensitivity of 48% in detecting cytomegalovirus retinitis that had been treated with systemic ganciclovir or foscarnet, or both. The assay did not give false-positive results in patients with vitreous hemorrhage or vitreous inflammation. Most important, the assay did not give false-positive results in AIDS patients with vitreous inflammation from causes other than cytomegalovirus retinitis. CONCLUSION: We have developed a sensitive and specific diagnostic assay that will assist in the diagnosis of cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗